User:ThomasYehYeh/沙盒/預覽：修订间差异
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{{Medical}} |
{{Medical}} |
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{{Infobox drug |
{{Infobox drug |
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| drug_name = |
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| Watchedfields = changed |
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| type = combo |
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| verifiedrevid = 464189839 |
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| component1 = 青蒿琥酯 |
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| image = Erythromycin A skeletal.svg |
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| class1 = 青蒿素 |
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| width = 200 |
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| component2 = 美爾奎寧 |
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| alt = |
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| class2 = 抗瘧藥 |
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| image2 = Erythromycin_3d_structure.png |
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| width2 = |
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| alt2 = |
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| caption = |
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<!-- Clinical data --> |
<!-- Clinical data --> |
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| pronounce |
| pronounce = |
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| tradename |
| tradename = |
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| Drugs.com |
| Drugs.com = |
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| MedlinePlus |
| MedlinePlus = |
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| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X --> |
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| DailyMedID = Erythromycin |
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| pregnancy_US = <!-- A/B/C/D/X --> |
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| pregnancy_AU = A |
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| pregnancy_category= |
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| pregnancy_AU_comment = <ref name=AG2015/> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| pregnancy_category = |
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| legal_AU_comment = |
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| routes_of_administration = [[口服給藥]]、[[靜脈注射]]、[[肌肉注射]]、[[外用藥物]]及[[眼藥水]]或眼藥膏 |
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| class = [[巨環內酯]]類抗生素 |
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| ATC_prefix = D10 |
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| ATC_suffix = AF02 |
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| ATC_supplemental = {{ATC|J01|FA01}} {{ATC|S01|AA17}} {{ATCvet|J51|FA01}} |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> |
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| legal_CA_comment = |
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| |
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| legal_DE_comment = |
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| legal_NZ = <!-- |
| legal_NZ = <!--Class A, B, C --> |
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| legal_status = |
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| legal_NZ_comment = |
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| routes_of_administration =[[口服給藥]] |
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| legal_UK = POM |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = |
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| legal_EU = |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = 在30%和65%之間（依酯類型而定） |
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| protein_bound = 90% |
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| metabolism = [[肝臟]] (其中有少於5%的為藥物原形) |
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| metabolites = |
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| onset = |
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| elimination_half-life = 1.5小時 |
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| duration_of_action = |
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| excretion = [[膽汁]] |
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<!-- Identifiers --> |
<!-- Identifiers --> |
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| CAS_number = 60473-87-2 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| ATCvet = |
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| CAS_number = 114-07-8 |
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| ATC_prefix = P01 |
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| CAS_supplemental = |
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| ATC_suffix = BF02 |
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| PubChem = 12560 |
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| PubChem = |
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| IUPHAR_ligand = 1456 |
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| DrugBank = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00199 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 12041 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 63937KV33D |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00140 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 42355 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 532 |
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| NIAID_ChemDB = |
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| PDB_ligand = ERY |
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| synonyms = |
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<!-- Chemical and physical data --> |
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| IUPAC_name = (3''R'',4''S'',5''S'',6''R'',7''R'',9''R'',11''R'',12''R'',13''S'',14''R'')-6-{[(2''S'',3''R'',4''S'',6''R'')-4-(Dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2''R'',4''R'',5''S'',6''S'')-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione |
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| C=37 | H=67 | N=1 | O=13 |
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| SMILES = CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)O)C)C)O)(C)O |
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| Jmol = none <!-- SMILES renders as flat --> |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C37H67NO13/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-/m1/s1 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = ULGZDMOVFRHVEP-RWJQBGPGSA-N |
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| density = |
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| density_notes = |
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| melting_point = |
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| melting_high = |
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| melting_notes = |
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| boiling_point = |
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| boiling_notes = |
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| solubility = |
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| sol_units = |
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| specific_rotation = |
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}} |
}} |
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'''青蒿琥酯/美爾奎寧'''（{{lang-en|Artesunate/mefloquin}}）是一種用於治療[[瘧疾]]的藥物。<ref name=WHO21st/>它是兩種[[抗瘧藥]] - [[青蒿琥酯]]和[[美爾奎寧]]組合而成的[[複方藥]]。<ref name=WHO21st/>建議專用於治療無併發症的[[惡性瘧原蟲]]導致的瘧疾。<ref name=WHO2014Use>{{cite book | vauthors = ((World Health Organization)) |title=The Selection and Use of Essential Medicines: Report of the WHO Expert Committee, 2013 (including the 18th WHO Model List of Essential Medicines and the 4th WHO Model List of Essential Medicines for Children) |year=2014|publisher=World Health Organization|isbn=9789241209854|page=43–4|hdl=10665/112729 | hdl-access=free }}</ref>藥物的攝取方式是經由[[口服給藥|口服]]。<ref name=WHO21st/> |
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'''紅黴素'''（{{lang-en|erythromycin}}）是一種[[抗生素]]，用於治療多種[[病原細菌]][[感染]],<ref name=AHFS2015/>包括如[[呼吸道感染]]、{{le|皮膚感染|Skin and skin structure infection}}、[[披衣菌感染]]、[[骨盆腔發炎]]和[[梅毒]]。<ref name=AHFS2015/>個體於[[妊娠|懷孕]]期間也可使用，以預防新生兒（neonate）的[[B型鏈球菌感染]]，<ref name=AHFS2015/>並用來改善{{le|胃排空延遲|Gastroparesis}}問題。<ref>{{cite journal | vauthors = Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L | title = Clinical guideline: management of gastroparesis | journal = The American Journal of Gastroenterology | volume = 108 | issue = 1 | pages = 18–37; quiz 38 | date = January 2013 | pmid = 23147521 | pmc = 3722580 | doi = 10.1038/ajg.2012.373 }}</ref>給藥途徑有[[靜脈注射]]和[[口服給藥|口服]]。<ref name=AHFS2015/>通常建議於剛[[出生]]的嬰兒眼睛塗抹紅黴素眼藥膏，以預防{{le|新生兒結膜炎|Neonatal conjunctivitis}}。<ref>{{cite journal | vauthors = Matejcek A, Goldman RD | title = Treatment and prevention of ophthalmia neonatorum | journal = Canadian Family Physician | volume = 59 | issue = 11 | pages = 1187–90 | date = November 2013 | pmid = 24235191 | pmc = 3828094 }}</ref> |
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使用後的副作用與單獨使用複方劑中兩種成分的相似。<ref name=WHO2014Use/>使用此複方劑是兩種藥物具有互補的特點 - 青蒿琥酯可快速殺滅血液中的瘧原蟲，迅速控制病情，美爾奎寧具有較長的半衰期，可以持續殺滅肝內的瘧原蟲，減少復發的可能性。此外，複方藥可降低治療時瘧原蟲可能具某種藥物抗藥性的問題。此藥物也有提供適合兒童的劑型。<ref name=WHO2014Use/> |
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使用此藥物常發生的副作用有腹部絞痛、[[嘔吐]]和[[腹瀉]]。<ref name=AHFS2015/>較嚴重的副作用有[[艱難擬梭菌感染]]、[[肝臟]]問題、[[長QT綜合症|QT間期延長]]和[[過敏反應]]。<ref name=AHFS2015/>對於[[青黴素]]過敏的個體，使用紅黴素通常屬於安全。<ref name=AHFS2015>{{cite web |title=Erythromycin|url=https://www.drugs.com/monograph/erythromycin.html |publisher=The American Society of Health-System Pharmacists |access-date=2015-08-01 |url-status=live|archive-url=https://web.archive.org/web/20150906031153/http://www.drugs.com/monograph/erythromycin.html|archive-date=2015-09-06}}</ref>個體於懷孕期間使用此藥物對於胎兒似無安全顧慮。<ref name=AG2015>{{cite web |title=Prescribing medicines in pregnancy database|url=http://www.tga.gov.au/hp/medicines-pregnancy.htm |work=Australian Government |date=2015-08-23|url-status=live|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|archive-date=2014-04-08}}</ref>雖然個體在[[母乳哺育]]期間使用，通常被認為對嬰兒安全，但母親在嬰兒出生後的前兩週使用此藥物可能會增加嬰兒發生[[幽門狹窄]]的風險。<ref name=Ric2013>{{cite book|vauthors=Hamilton RJ|title=Tarascon pocket pharmacopoeia|date=2013|publisher=Jones & Bartlett Learning|location=[Sudbury, Mass.]|isbn=9781449673611|page=72|edition=2013 delux lab-coat ed., 14th|url=https://books.google.com/books?id=zJay-fZCFGgC&pg=PA72|access-date=2017-09-09|archive-date=2020-08-01|archive-url=https://web.archive.org/web/20200801095144/https://books.google.com/books?id=zJay-fZCFGgC&pg=PA72|url-status=live}}</ref><ref name="Kong2013">{{cite journal | vauthors = Kong YL, Tey HL | title = Treatment of acne vulgaris during pregnancy and lactation | journal = Drugs | volume = 73 | issue = 8 | pages = 779–87 | date = June 2013 | pmid = 23657872 | doi = 10.1007/s40265-013-0060-0 | s2cid = 45531743 }}</ref>如果新生兒在此期間直接服用，也有類似風險。<ref name=Erythromycin>{{cite journal | vauthors = Maheshwai N | title = Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis? | journal = Archives of Disease in Childhood | volume = 92 | issue = 3 | pages = 271–3 | date = March 2007 | pmid = 17337692 | pmc = 2083424 | doi = 10.1136/adc.2006.110007 | url = http://adc.bmj.com/content/92/3/271| archive-url = https://web.archive.org/web/20121107021907/http://adc.bmj.com/content/92/3/271 | url-status = live | archive-date = 2012-11-07 }}</ref>紅黴素屬於[[巨環內酯]]類抗生素家族，透過減少細菌蛋白質產生而發揮作用。<ref name=AHFS2015/> |
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青蒿琥酯/美爾奎寧於2008年首次在[[巴西]]取得核准用於醫療用途。<ref name=St2012>{{cite book| vauthors = Staines HM, Krishna S |author-link2=Sanjeev Krishna|title=Treatment and Prevention of Malaria: Antimalarial Drug Chemistry, Action and Use|date=2012|publisher=Springer Science & Business Media|isbn=9783034604802|page=239|url=https://books.google.com/books?id=IXWOXUpylO8C&pg=PA239|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220161905/https://books.google.ca/books?id=IXWOXUpylO8C&pg=PA239|archive-date=2016-12-20}}</ref>它已納入[[世界衛生組織基本藥物標準清單]]之中。<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>巴西、[[印度]]和[[馬來西亞]]均核准將此藥物用於醫療用途，<ref name=WHO2014Use/>但其並未取得[[美國食品藥物管理局]]（FDA）的核准，也未在美國販售。<ref>{{cite book| vauthors = Sanford CA, Jong EC, Pottinger PS |title=The Travel and Tropical Medicine Manual|date=2016|publisher=Elsevier Health Sciences|isbn=9780323417426|page=307|edition=5|url=https://books.google.com/books?id=jyTRDAAAQBAJ&pg=PA307|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220162041/https://books.google.ca/books?id=jyTRDAAAQBAJ&pg=PA307|archive-date=2016-12-20}}</ref> |
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==醫療用途== |
==醫療用途== |
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青蒿琥酯/美爾奎寧種是推薦在[[東南亞]]使用的治療瘧疾藥物，而如複方藥[[青蒿琥酯/阿莫待奎]]、[[蒿甲醚/苯芴醇]]、{{le|青蒿琥酯/磺胺多辛/乙胺嘧啶|artesunate/sulfadoxine/pyrimethamine}}則通常是在[[非洲]]的首選治療瘧疾藥物。<ref>{{cite book| vauthors = Marcondes CB |title=Arthropod Borne Diseases|date=2016|publisher=Springer|isbn=9783319138848|page=35|url=https://books.google.com/books?id=Qs55DQAAQBAJ&pg=PA335|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220163853/https://books.google.ca/books?id=Qs55DQAAQBAJ&pg=PA335|archive-date=2016-12-20}}</ref> |
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紅黴素可針對引起皮膚和上呼吸道感染的病原細菌（包括[[鏈球菌屬]]、[[葡萄球菌屬]]、[[嗜血桿菌屬]]和[[棒桿菌屬]]）進行治療。一些具有醫學意義的[[最小抑菌濃度]]數據如下列：<ref name = "www.toku-e.com">{{cite web | url = http://www.toku-e.com/Assets/MIC/Erythromycin.pdf | title = Erythromycin Susceptibility and Minimum Inhibitory Concentration (MIC) Data | publisher = TOKU-E | access-date = 2014-02-26 | archive-date = 2015-05-09 | archive-url = https://web.archive.org/web/20150509091111/http://www.toku-e.com/Assets/MIC/Erythromycin.pdf | url-status = live }}</ref> |
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==特定群體== |
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*[[流感嗜血桿菌]]：0.015至256微克/毫升 |
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===懷孕=== |
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*[[金黃色葡萄球菌]]：0.023至1024微克/毫升 |
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有小型的實驗，研究結果並沒明確支持青蒿琥酯/美爾奎寧對孕婦安全的證據。孕婦使用此藥物應該在醫生的密切監控下進行，權衡利弊後做出最適合的治療方案。目前建議孕婦避免使用含有美爾奎寧的製劑，除非其他藥物的治療無效。<ref>{{cite journal |last1= Valea |first1=Innocent |last2=Tinto |first2=Halidou |date=2014-06-02 |title= Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC4130382/ |journal= Journal of Antimicrobial Chemotherapy |volume=69 |issue=9 |pages=2499-2507 |doi= 10.1093/jac/dku154|access-date=2024-10-19}}</ref> |
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*[[化膿性鏈球菌]]：0.004至256微克/毫升 |
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*{{le|微小棒狀桿菌|Corynebacterium minutissimum}}：0.015至64微克/毫升 |
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===母乳哺育=== |
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由於藥物有促進胃腸蠕動的作用，有助於治療胃排空延遲。它已被證明可改善重症患者的餵養耐受性問題。<ref>{{cite journal | vauthors = Lewis K, Alqahtani Z, Mcintyre L, Almenawer S, Alshamsi F, Rhodes A, Evans L, Angus DC, Alhazzani W | title = The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials | journal = Critical Care | volume = 20 | issue = 1 | pages = 259 | date = August 2016 | pmid = 27527069 | pmc = 4986344 | doi = 10.1186/s13054-016-1441-z | doi-access = free }}</ref>進行[[上消化道內視鏡]]檢查前可進行靜脈注射紅黴素，以協助清除胃內容物，提高診斷準確性和後續管理。<ref>{{cite journal | vauthors = Lewis K, Alqahtani Z, Mcintyre L, Almenawer S, Alshamsi F, Rhodes A, Evans L, Angus DC, Alhazzani W | title = The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials | journal = Critical Care | volume = 20 | issue = 1 | pages = 259 | date = August 2016 | pmid = 27527069 | pmc = 4986344 | doi = 10.1186/s13054-016-1441-z | doi-access = free }}</ref> |
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進行[[母乳哺育]]的個體單獨使用青蒿琥酯，或是美爾奎寧，對於嬰兒看來均無安全問題。<ref>{{cite web|title=Artesunate use while Breastfeeding {{!}} Drugs.com|url=https://www.drugs.com/breastfeeding/artesunate.html|website=www.drugs.com|access-date=2016-12-07|url-status=live|archive-url=https://web.archive.org/web/20161220222313/https://www.drugs.com/breastfeeding/artesunate.html|archive-date=2016-12-20}}</ref><ref name=CDC2019>{{cite web|title=Mefloquine|work=Medicines for the Prevention of Malaria While Traveling|publisher=[[Centers for Disease Control and Prevention]]|location=Atlanta, Georgia|year=2019|url=https://www.cdc.gov/malaria/resources/pdf/fsp/drugs/mefloquine.pdf|access-date=2019-03-30}}</ref> |
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==禁忌症== |
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對於青蒿琥酯成分嚴重過敏的個體禁用含有此成分的複方藥，<ref>{{cite journal | vauthors = Hess KM, Goad JA, Arguin PM | title = Intravenous artesunate for the treatment of severe malaria | journal = The Annals of Pharmacotherapy | volume = 44 | issue = 7–8 | pages = 1250–1258 | date = 1 January 2010 | pmid = 20551300 | doi = 10.1345/aph.1M732 | url = https://works.bepress.com/goad/3/ | url-status = live | s2cid = 23946665 | archive-url = https://web.archive.org/web/20161110043829/https://works.bepress.com/goad/3/ | archive-date = 10 November 2016 }}</ref>於青蒿琥酯給藥時應避免同時使用會抑制[[細胞色素P450]]家族中{{le|CYP2A6|CYP2A6}}的藥物（CYP2A6負責代謝多種藥物，包括青蒿琥酯。如果服用這類有抑制作用的藥物，可能會影響青蒿琥酯在人體的代謝，導致其濃度過高，增加副作用的風險）。前述抑制藥物包括[[胺碘酮]]、{{le|地昔帕明|desipramine}}、[[異煙肼]]、[[酮康唑]]、{{le|來曲唑|letrozole}}、{{le|甲氧沙林|methoxsalen}} 和[[反苯環丙胺]]。<ref>{{Cite web|url=http://www.wipo.int/export/sites/www/research/en/data/sanofi/marketed_products/Artesunate_and_Amodiquine.pdf|title=Artesunate Amodiaquine Winthrop (artesunate, amodiaquine) [summary of product characteristics]|publisher=Sanofi-Aventis|url-status=live|archive-url=https://web.archive.org/web/20161024090154/http://www.wipo.int/export/sites/www/research/en/data/sanofi/marketed_products/Artesunate_and_Amodiquine.pdf|archive-date=2016-10-24}}</ref> |
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而曾有[[癲癇發作]]，或是近期有[[精神障礙]]的個體禁用含有美爾奎寧的製劑。<ref name="AHFS">{{cite web|title=Lariam|url=https://www.drugs.com/monograph/lariam.html|work=The American Society of Health-System Pharmacists|access-date=2011-04-03|url-status=live|archive-url=https://web.archive.org/web/20120107150658/http://www.drugs.com/monograph/lariam.html|archive-date=2012-01-07}}</ref> |
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===市售藥物配方=== |
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[[File:000719lg Enteric coated erythomycin.jpg|thumb|[[亞培]]製藥出品的紅黴素腸溶膠囊。]] |
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==交互作用== |
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紅黴素有{{le|腸溶|enteric coating}}片劑、緩釋膠囊、口服懸浮液、眼藥水、軟膏、凝膠、腸溶膠囊、非腸溶片、非腸溶膠囊及注射劑。 |
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根據一項小型研究，證明青蒿素和美爾奎寧之間的藥物交互作用並不嚴重。<ref>{{cite journal |last1= Lefèvre|first1=Gilbert |last2= Bindschedler |
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用於口服的紅黴素製劑有：<ref name=drugs.com>{{cite web | url = https://www.drugs.com/cons/erythromycin-oral-parenteral.html | title = Erythromycin Oral, Parenteral Advanced Patient Information | work = Drugs.com | url-status = live | archive-url = https://web.archive.org/web/20091130183915/http://www.drugs.com/cons/erythromycin-oral-parenteral.html | archive-date = 2009-11-30 }}</ref> |
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|first2=Margaretha |date=April 2000 |title= Pharmacokinetic interaction trial between co-artemether and mefloquine |
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*紅黴素鹼（膠囊、片劑） |
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|url=https://www.sciencedirect.com/science/article/abs/pii/S0928098700000609 |journal= European Journal of Pharmaceutical Sciences |
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*紅黴素酯（膠囊、口服懸浮液、片劑），於懷孕期的個體禁用<ref name="pmid16888612">{{cite journal | vauthors = Workowski KA, Berman SM | title = Sexually transmitted diseases treatment guidelines, 2006 | journal = MMWR: Recommendations and Reports | volume = 55 | issue = RR-11 | pages = 1–94 | date = August 2006 | pmid = 16888612 | doi = | url = https://www.cdc.gov/std/treatment/2006/toc.htm | archive-url = https://web.archive.org/web/20100211154655/http://www.cdc.gov/std/treatment/2006/toc.htm | archive-date=2010-02-11}}</ref> |
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|volume=10 |issue=2 |pages=141-151 |doi=10.1016/S0928-0987(00)00060-9 |access-date=2024-10-19}}</ref> |
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*乙基琥珀酸紅黴素（口服懸浮液、片劑） |
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*硬脂酸紅黴素（口服懸浮液、片劑） |
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==藥物開發歷史== |
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用於注射的製劑有：<ref name=drugs.com/> |
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此複方劑由非營利性藥物研究和開發組織{{le|被忽視疾病藥物倡議|Drugs for Neglected Diseases Initiative}}（DNDi）開發。<ref name="DNDi"/> |
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*葡萄糖紅黴素 |
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*乳糖酸紅黴素 |
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傳統上藥物通常經由製藥公司自行研發，研究和開發成本最終通過藥物銷售來回收。開發用於治療被忽視的熱帶疾病的藥物不能只考慮市場的獲利，需要一種超越市場驅動的研究和開發思維。<ref name="DNDi"/> |
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用於眼科的製劑有： |
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*紅黴素鹼（軟膏） |
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DNDi於全球各大洲建立起合作夥伴關係，將配方、控制和生產到臨床試驗以及產品註冊的問題全部解決，開發出此種安全有效的組合治療藥物，以供應供資源匱乏地區的患者使用。而藥物製造從巴西的Farmanguinhos/Fiocruz（Institute of Pharmaceutical Technology）技術移轉到[[印度]]的跨國製藥與生技公司[[Cipla|西普拉製藥]]，更是創下[[開發中國家]]間的首例。通過這樣的合作，開發中國家在知識和技術方面得以互補，共同提升整體能力。。<ref name="DNDi"/> |
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==不良影響== |
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由於紅黴素是{{le|胃動素|motilin}}激動劑，使用後會常發生腹瀉、[[噁心]]、[[腹痛]]和嘔吐等胃腸道紊亂問題。<ref name="pmid8470625">{{cite journal | vauthors = Weber FH, Richards RD, McCallum RW | title = Erythromycin: a motilin agonist and gastrointestinal prokinetic agent | journal = The American Journal of Gastroenterology | volume = 88 | issue = 4 | pages = 485–90 | date = April 1993 | pmid = 8470625 }}</ref> |
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青蒿素和美爾奎寧這兩種藥物對治療無併發症惡性瘧原蟲導致的瘧疾已有長時間的經驗，也有良好的安全性。把這兩種藥結合，以固定劑量的複方形式給藥，可讓病人更易按時服藥，同時也能減少瘧原蟲產生抗藥性的風險。<ref name="DNDi">{{cite journal |last1= Wells|first1=Susan |last2= Diap |
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較嚴重的副作用有QT間期延長的[[心律不整]]問題，包括{{le|扭轉型尖峰|orsades de pointes}}（一種特定類型的心律不整），還有可逆性耳[[聾]]。過敏反應有[[蕁麻疹]]及[[過敏性休克]]等。罕見的副作用有{{le|膽汁淤積| Cholestasis}}和[[史蒂芬斯－強森症候群]]。<ref>{{cite book |title=Meyler's Side Effects of Drugs |publisher=Elsevier |year=2016 |pages=99–108 |url= | veditors = Aronson JK |chapter=Erythromycin |edition=Sixteenth |doi=10.1016/B978-0-444-53717-1.00698-3 |isbn=9780444537164 |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780444537171006983}}</ref> |
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|first2=Graciela|date=2013-02-21|title= The story of artesunate-mefloquine (ASMQ), innovative partnerships in drug development: case study |
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|url=https://pubmed.ncbi.nlm.nih.gov/23433060/ |journal= Malaria Journal|volume= |issue= |pages= |doi=10.1186/1475-2875-12-68 |access-date=2024-10-19}}</ref> |
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== 參見 == |
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研究工作同時顯示有支持和反對幽門狹窄與產前和產後接觸紅黴素之間關聯的證據。<ref name = "Briggs_2011">{{cite book |vauthors=Briggs GG, Freeman RK, Yaffe SJ |title=Drugs in pregnancy and lactation : a reference guide to fetal and neonatal risk |date=2011 |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-1-60831-708-0 |edition=9th |chapter=Erythromycin |chapter-url=https://books.google.com/books?id=OIgTE4aynrMC&q=erythromycin&pg=PA512 |access-date=2021-10-20 |archive-date=2022-05-23 |archive-url=https://web.archive.org/web/20220523131602/https://books.google.com/books?id=OIgTE4aynrMC&q=erythromycin&pg=PA512 |url-status=live }}</ref> 接觸紅黴素（尤其是長期療程劑量，以及透過母乳哺育）與小嬰兒幽門狹窄的可能性增加有關聯。<ref name="pmid17337692">{{cite journal | vauthors = Maheshwai N | title = Are young infants treated with erythromycin at risk for developing hypertrophic pyloric stenosis? | journal = Archives of Disease in Childhood | volume = 92 | issue = 3 | pages = 271–3 | date = March 2007 | pmid = 17337692 | pmc = 2083424 | doi = 10.1136/adc.2006.110007 }}</ref><ref name="pmid24618148">{{cite journal | vauthors = Lund M, Pasternak B, Davidsen RB, Feenstra B, Krogh C, Diaz LJ, Wohlfahrt J, Melbye M | title = Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study | journal = BMJ | volume = 348 | pages = g1908 | date = March 2014 | pmid = 24618148 | pmc = 3949411 | doi = 10.1136/bmj.g1908 }}</ref>用於治療年幼嬰兒餵食不耐受的紅黴素與嬰兒肥厚性幽門狹窄無關聯。<ref name="pmid17337692"/> |
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* {{le|雙氫青蒿素/哌喹|Dihydroartemisinin/piperaquine}} |
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== 參考文獻 == |
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紅黴素與孕婦可逆性{{le|肝毒性|hepatotoxicity}}有關聯，表現為[[天冬氨酸氨基转移酶|天門冬胺酸胺基轉移酶]]（又稱血清麩胺酸草醯乙酸轉胺酶）水平升高，因此不建議於懷孕期間的婦女使用。一些證據顯示其他族群也發生類似的肝毒性。<ref>{{cite journal | vauthors = McCormack WM, George H, Donner A, Kodgis LF, Alpert S, Lowe EW, Kass EH | title = Hepatotoxicity of erythromycin estolate during pregnancy | journal = Antimicrobial Agents and Chemotherapy | volume = 12 | issue = 5 | pages = 630–5 | date = November 1977 | pmid = 21610 | pmc = 429989 | doi = 10.1128/AAC.12.5.630 }}</ref> |
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{{reflist|2}} |
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== 外部連結 == |
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紅黴素也會影響[[中樞神經系統]]，引起[[精神病 (症状)|精神病]]反應、作[[惡夢]]和{{le|夜間盜汗|night sweat}}。<ref name="BCFI"/> |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/artesunate%20mixture%20with%20mefloquine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Artesunate mixture with mefloquine }} |
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==藥物交互作用== |
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紅黴素經由[[細胞色素P450]]系統的酶，特別是如{{le|CYP3A|CYP3A}}[[蛋白質超家族]]的[[同工酶]]代謝。<ref name="pmid1732074">{{cite journal | vauthors = Hunt CM, Watkins PB, Saenger P, Stave GM, Barlascini N, Watlington CO, Wright JT, Guzelian PS | title = Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol | journal = Clinical Pharmacology and Therapeutics | volume = 51 | issue = 1 | pages = 18–23 | date = January 1992 | pmid = 1732074 | doi = 10.1038/clpt.1992.3 | hdl = 2027.42/109905 | s2cid = 28056649 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/109905/1/cptclpt19923.pdf | hdl-access = free | access-date = 2019-08-29 | archive-date = 2021-08-28 | archive-url = https://web.archive.org/web/20210828075533/https://deepblue.lib.umich.edu/bitstream/handle/2027.42/109905/cptclpt19923.pdf;jsessionid=E4EB0A4C0D1D5A07533C041190B23FA0?sequence=1 | url-status = live }}</ref>某些藥物（例如[[地塞米松]]）可誘導或抑制CYP3A酶的活性，而影響許多不同藥物（包括紅黴素）的代謝。如果其他CYP3A基質（會被CYP3A分解的藥物），例如[[辛伐他汀]](Zocor)、{{le|洛伐他汀|lovastatin }}(Mevacor) 或[[阿托伐他汀]](Lipitor)與紅黴素同時服用，用藥者體內基質的濃度會增加，通常會引起不良反應。一種須注意的藥物交互作用涉及紅黴素和辛伐他汀，導致辛伐他汀濃度升高和產生[[橫紋肌溶解症]]的可能性。另一組CYP3A4基質是用於治療[[偏頭痛]]的藥物，例如[[麥角胺]]和{{le|二氫麥角胺|dihydroergotamine}}，如果與紅黴素合併使用，其不良反應可能會更為明顯。<ref name="BCFI">{{cite web | url = http://www.bcfi.be/GGR/MPG/MPG_KABA.cfm | title = Erythromycine | work = Belgisch Centrum voor Farmacotherapeutische Informatie | url-status = live | archive-url = https://web.archive.org/web/20151006100756/http://www.bcfi.be/GGR/MPG/MPG_KABA.cfm | archive-date = 2015-10-06 }}</ref> |
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由於早期發生有關猝死的病例報告，而促使醫界進行一項大型研究，證實在服用透過干擾CYP3A4而延長紅黴素代謝藥物（如[[維拉帕米]]或[[地爾硫䓬]]）的患者中，紅黴素與[[心室性心搏過速]]和心源性猝死之間存在關聯。<ref>{{cite journal | vauthors = Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM | title = Oral erythromycin and the risk of sudden death from cardiac causes | journal = The New England Journal of Medicine | volume = 351 | issue = 11 | pages = 1089–96 | date = September 2004 | pmid = 15356306 | doi = 10.1056/NEJMoa040582 | doi-access = free }}</ref>因此使用這些藥物或會延長QT間期的藥物的個體不應服用紅黴素。其他不應與紅黴素同時服用藥物包括有{{le|特非那定|terfenadine}}（Seldane、Seldane-D）、<ref>{{cite web |url=https://www.drugs.com/drug-interactions/erythromycin-with-terfenadine-1009-0-2164-0.html?professional=1 |title=Drug Interactions between erythromycin and terfenadine |access-date=2023-12-21 |website=Drugs.com}}</ref>{{le|阿司咪唑|astemizole}}（Hismanal）、<ref>{{cite web |url=https://www.drugs.com/drug-interactions/astemizole-with-erythromycin-271-0-1009-0.html?professional=1 |title=Drug Interactions between astemizole and erythromycin |access-date= 2023-12-21 |website=Drugs.com}}</ref>{{le|西沙必利|cisapride}}<ref>{{cite journal | vauthors = Michalets EL, Williams CR | title = Drug interactions with cisapride: clinical implications | journal = Clinical Pharmacokinetics | volume = 39 | issue = 1 | pages = 49–75 | date = July 2000 | pmid = 10926350 | doi = 10.2165/00003088-200039010-00004 | s2cid = 41704853 }}</ref>（Propulsid，因會延長QT間期而在許多國家被撤銷許可）和[[雙氟苯丁哌啶苯並咪唑酮]](Orap)。<ref>{{cite web |url=https://gpnotebook.com/pages/ear-nose-and-throat/erythromycin/interactions |title=Erythromycin Interactions |date=2020-12-20 |access-date= 2023-12-21 |website=GPnotebook |archive-url=https://web.archive.org/web/20231221161502/https://gpnotebook.com/pages/ear-nose-and-throat/erythromycin/interactions |archive-date= 2023-12-21 |url-status=live}}</ref>也有證據顯示紅黴素會與用於治療[[氣喘]]的[[茶鹼]]發生交互作用。<ref>{{cite web |url=https://www.drugs.com/drug-interactions/erythromycin-with-theophylline-1009-0-2177-0.html?professional=1 |title=Drug Interactions between erythromycin and theophylline |access-date=2023-12-21 |website=Drugs.com |archive-url=https://web.archive.org/web/20231221104101/https://www.drugs.com/drug-interactions/erythromycin-with-theophylline-1009-0-2177-0.html?professional=1 |archive-date=2023-12-21 |url-status=live}}</ref> |
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紅黴素和[[去氧羥四環素]]併用時可產生協同作用，殺死細菌（[[大腸桿菌]]）的效力比兩種藥物個別使用的總和更高。這種協同關係只具暫時性，於約72小時後會轉變為拮抗關係，其中50/50的兩種藥物組合殺死細菌的數量比單獨施用兩種藥物為少。。<ref>{{cite journal | vauthors = Pena-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P, Schulenburg H, Beardmore R | title = When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition | journal = PLOS Biology | volume = 11 | issue = 4 | pages = e1001540 | date =2013-04-23 | pmid = 23630452 | pmc = 3635860 | doi = 10.1371/journal.pbio.1001540 | doi-access = free }}</ref> |
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由於紅黴素對腸道菌群的影響，可能會改變[[複方口服避孕藥]]的有效性。一篇研究報告提出當紅黴素與某些口服避孕藥併用時，[[雌二醇]]和{{le|地諾孕素|dienogest}}的最大血清濃度和[[曲線下面積 (藥物代謝動力學)|曲線下面積]]會增加（導致避孕效果降低及副作用增加）。<ref>{{cite journal | vauthors = Blode H, Zeun S, Parke S, Zimmermann T, Rohde B, Mellinger U, Kunz M | title = Evaluation of the effects of rifampicin, ketoconazole and erythromycin on the steady-state pharmacokinetics of the components of a novel oral contraceptive containing estradiol valerate and dienogest in healthy postmenopausal women | language = en | journal = Contraception | volume = 86 | issue = 4 | pages = 337–44 | date = October 2012 | pmid = 22445438 | doi = 10.1016/j.contraception.2012.01.010 | url = https://www.contraceptionjournal.org/article/S0010-7824(12)00041-8/abstract | access-date = 2019-08-02 | archive-date = 2021-08-28 | archive-url = https://web.archive.org/web/20210828075535/https://www.contraceptionjournal.org/article/S0010-7824%2812%2900041-8/fulltext | url-status = live }}</ref><ref>{{cite journal | vauthors = Simmons KB, Haddad LB, Nanda K, Curtis KM | title = Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review | language = en | journal = American Journal of Obstetrics and Gynecology | volume = 218 | issue = 1 | pages = 88–97.e14 | date = January 2018 | pmid = 28694152 | doi = 10.1016/j.ajog.2017.07.003 | s2cid = 36567820 | url = https://www.ajog.org/article/S0002-9378(17)30845-1/abstract | access-date = 2019-08-02 | archive-date = 2021-08-28 | archive-url = https://web.archive.org/web/20210828075543/https://www.ajog.org/article/S0002-9378%2817%2930845-1/fulltext | url-status = live }}</ref> |
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紅黴素是細胞色素P450系統的抑制劑，表示它可對該系統代謝的其他藥物（例如[[華法林]]）的濃度產生快速影響。<ref>{{cite journal | vauthors = Westphal JF | title = Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin | journal = British Journal of Clinical Pharmacology | volume = 50 | issue = 4 | pages = 285–295 | date = October 2000 | pmid = 11012550 | pmc = 2015000 | doi = 10.1046/j.1365-2125.2000.00261.x }}</ref> |
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==藥理學== |
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===作用機轉=== |
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紅黴素具有抑制細菌活性或抑制細菌生長的能力，尤其是在較高濃度的情況下。<ref name = "Trevor_2010">{{cite book | chapter = Section VIII: Chemotherapeutic Drugs; Chapter 44: Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins | pages = 389–396 | veditors = Trevor AJ, Katzung BG, Masters SB |title = Katzung & Trevor's Pharmacology: Examination & Board Review |date=2010 |publisher=McGraw-Hill Medical |location=New York |isbn=978-0-07-170155-6 |edition=9th}}</ref>它透過與細菌[[核糖體核糖核酸|rRNA]]複合物的50s亞基結合，細菌的蛋白質合成以及隨後對生命或複製非常重要的結構和功能過程會受到抑制。紅黴素干擾氨酰易位，<ref name="Trevor_2010"/>阻止結合在rRNA複合物A位點的[[轉運核糖核酸|tRNA]]轉移到rRNA複合物P位點。因此細菌的蛋白質合成過程為之中斷（結果為蛋白質合成停滯、細胞功能失調及細胞死亡）。<ref>{{cite web |url=https://www.sigmaaldrich.com/SE/en/product/sial/e6376 |title=Erythromycin |access-date=2023-12-21 |website=Sigma-Aldrich}}</ref> |
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紅黴素透過與胃動素受體結合來增加腸道蠕動，因此除具抗菌特性外，還是一種胃動素受體激動劑，而可作為胃排空刺激劑。<ref>{{cite book |title=Gastroparesis: Pathophysiology, Clinical Presentation, Diagnosis and Treatment | vauthors = Parkman HP |publisher=Academic Press |year=2021 |pages=323–339 |chapter=Chapter 24 - Prokinetic agents for gastroparesis |doi=10.1016/B978-0-12-818586-5.00024-7 |isbn=9780128185865 |quote=Erythromycin has prokinetic effects because it is a motilin receptor agonist in addition to being an antibiotic. [...] When given intravenously, erythromycin is a potent stimulant of gastric emptying among the available prokinetic drugs. |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780128185865000247}}</ref> |
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===藥物動力學=== |
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紅黴素易被胃酸滅活，因此口服製劑多以腸溶衣包裹或製成藥學上更穩定的鹽類或酯類，例如紅黴素乙基琥珀酸酯。人體能很快吸收紅黴素，並擴散到大多數組織和[[吞噬細胞]]。含高濃度紅黴素的吞噬細胞會主動轉運至感染部位，在主動吞噬作用時，會釋放大量高濃度紅黴素而發揮作用。<ref>{{cite journal | vauthors = Lebel M | title = Pharmacokinetic properties of clarithromycin: A comparison with erythromycin and azithromycin | journal = The Canadian Journal of Infectious Diseases | volume = 4 | issue = 3 | pages = 148–152 | date = May 1993 | pmid = 22346438 | pmc = 3250788 | doi = 10.1155/1993/168061 | doi-access = free }}</ref> |
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===代謝=== |
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大多數紅黴素在肝臟中經由肝臟酵素CYP3A4進行[[脫甲基化]]代謝。代謝物主要經由膽汁排除，受腎臟排泄的數量很少，排除的原形藥物佔比有2%～15%。紅黴素的[[生物半衰期]]為1.5至2.0小時，對於末期腎病患者為5至6小時。血清中紅黴素濃度於服藥後4小時可達到峰值，紅黴素乙基琥珀酸酯會在給藥後0.5-2.5小時達到峰值。服藥同時也進行飲食時，達到血藥濃度峰值的時間會被延遲。<ref name = "Edmunds_2009">{{cite book |vauthors=Edmunds MW, Mayhew MS |title=Pharmacology for the primary care provider |date=2009 |location=Saint Louis, Missouri | publisher = Elsevier Health Sciences |isbn=978-0-323-06316-6 |edition=Third |chapter=Chapter 61: Macrolides |pages=658–662 (661) |chapter-url=https://books.google.com/books?id=9JtgGU0fkggC&pg=PA661 |access-date=2022-03-03 |archive-date=2022-05-23 |archive-url=https://web.archive.org/web/20220523131602/https://books.google.com/books?id=9JtgGU0fkggC&pg=PA661 |url-status=live }}; {{cite book | vauthors = Kirst HA, Sides GD | date = 1993 | chapter = Chapter 28: Erythromycin | veditors = Bryskier A, Butzler JP, Neu HC, Tulkens | title = The Macrolides | publisher = Arnette-Blackwell | location = Oxford UK }}</ref> |
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紅黴素會穿過[[胎盤]]並進入母乳。[[美國兒科學會]]認定個體於[[母乳哺育]]期間使用紅黴素對於嬰兒並無安全上顧慮。<ref name="urlwww.breastfeedingmadesimple.com">{{cite journal | title = Transfer of drugs and other chemicals into human milk | journal = Pediatrics | volume = 108 | issue = 3 | pages = 776–89 | date = September 2001 | pmid = 11533352 | doi = 10.1542/peds.108.3.776 | author1 = American Academy of Pediatrics Committee on Drugs | doi-access = free }}</ref>懷孕個體在紅黴素吸收方面已被證明會有差別，通常的藥物濃度會低於非懷孕的個體。<ref name="Philipson_1976">{{cite journal | vauthors = Philipson A, Sabath LD, Charles D | title = Erythromycin and clindamycin absorption and elimination in pregnant women | journal = Clinical Pharmacology and Therapeutics | volume = 19 | issue = 1 | pages = 68–77 | date = January 1976 | pmid = 1245094 | doi = 10.1002/cpt197619168 | s2cid = 7573420 }}</ref><ref name = "Briggs_2011" /> |
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==化學== |
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===成分=== |
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標準級紅黴素主要由四種相關化合物組成，稱為紅黴素A、B、C 和D。這些化合物的含量會因生產批次而有所不同。研究發現紅黴素A具有最強的抗菌活性，其次是紅黴素B。紅黴素C和D的活性約為紅黴素A的一半。<ref name = "www.toku-e.com"/><ref name="pmid4091529">{{cite journal | vauthors = Kibwage IO, Hoogmartens J, Roets E, Vanderhaeghe H, Verbist L, Dubost M, Pascal C, Petitjean P, Levol G | title = Antibacterial activities of erythromycins A, B, C, and D and some of their derivatives | journal = Antimicrobial Agents and Chemotherapy | volume = 28 | issue = 5 | pages = 630–3 | date = November 1985 | pmid = 4091529 | pmc = 176346 | doi = 10.1128/aac.28.5.630 }}</ref>其中一些相關化合物已被純化，可進行個別研究。 |
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===合成=== |
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人們在發現紅黴素A及其抗菌活性後的三十年裡進行過許多實驗室合成嘗試。最後由美國[[有機化學]]家[[罗伯特·伯恩斯·伍德沃德|勞勃·伯恩斯·伍華德]]成功合成紅黴素A，並於1981年將研究成果發表。<ref>{{cite journal | vauthors = Woodward RB, Logusch E, Nambiar KP, Sakan K, Ward DE, Au-Yeung BW, Balaram P, Browne LJ, Card PJ, Chen CH | date = June 1981 | title = Asymmetric Total Synthesis of Erythromycin. 1. Synthesis of an Erythronolide A Seco Acid Derivative via Asymmetric Induction | journal = Journal of the American Chemical Society | volume = 103 | issue = 11| pages = 3210–3213 | doi = 10.1021/ja00401a049 }}</ref><ref>{{cite journal | vauthors = Woodward RB, Au-Yeung BW, Balaram P, Browne LJ, Ward DE, Au-Yeung BW, Balaram P, Browne LJ, Card PJ, Chen CH | year = 1981 | title = Asymmetric Total Synthesis of Erythromycin. 2. Synthesis of an Erythronolide A Lactone System | journal = Journal of the American Chemical Society | volume = 103 | issue = 11| pages = 3213–3215 | doi = 10.1021/ja00401a050 }}</ref><ref>{{cite journal | vauthors = Woodward RB, Logusch E, Nambiar KP, Sakan K, Ward DE, Au-Yeung BW, Balaram P, Browne LJ, Card PJ, Chen CH | date = June 1981 | title = Asymmetric Total Synthesis of Erythromycin. 3. Total Synthesis of Erythromycin | journal =Journal of the American Chemical Society | volume = 103 | issue = 11| pages = 3215–3217 | doi = 10.1021/ja00401a051 }}</ref> |
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==歷史== |
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一位服務於[[禮來]]製藥在[[菲律賓]]分支機構的當地醫生 - {{le|阿韋拉多·阿吉拉爾|Abelardo Aguilar}} - 於1949年將一些土壤樣本寄給美國禮來製藥。阿吉拉爾設法從樣本中發現的一種紅鏈黴菌（紅糖多孢菌）的代謝物中分離出紅黴素。阿吉拉爾並未因為此發現而得到進一步的榮譽或補償。<ref>{{cite news |url=https://opinion.inquirer.net/123626/drugs-and-rights |title=Drugs and rights |date=2019-08-30 |access-date=2023-12-21 |newspaper=[[Philippine Daily Inquirer]] | vauthors = Tan ML }}</ref> |
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禮來製藥於1953年獲得此化合物的專利保護。.<ref>{{cite patent | country = US | number = 2653899 | title = Erythromycin, its salts, and method of preparation | inventor = Bunch RL, Mcguire JM | assign1 = Eli Lilly and Company | pubdate = 1953-09-29 | postscript = . }}</ref>該產品於1952年以Ilosone品牌投入商業市場（以最初採集該產品的菲律賓[[怡朗省]]命名）。紅黴素以前也稱為怡朗黴素（Ilotycin）。[[克拉黴素]]是由[[日本]]藥廠[[大正製藥]]的科學家於1970年代發明，用來克服紅黴素在酸性環境下容易分解或失效的性質。<ref>{{cite book | vauthors = Greenwood D |url=https://books.google.com/books?id=i4_FZHmzjzwC&pg=PA239 |title=Antimicrobial drugs: chronicle of a twentieth century medical triumph |date=2008 |publisher=Oxford university press |isbn=978-0-19-953484-5 |location=New York |pages=239}}</ref> |
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==社會與文化== |
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===經濟學=== |
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紅黴素已有[[通用名藥物]]在市面流通。<ref name=Ric2013 /> |
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在美國，紅黴素500毫克片劑的一片價格從0.7美元上漲至7美元。<ref name="increase">{{cite web | vauthors = Stahl S | date = 2014-09-26 | url = http://philadelphia.cbslocal.com/2014/09/26/health-generic-drugs-prices-increasing/ | title = Health: Generic Drugs Prices Increasing | archive-url = https://web.archive.org/web/20160409212651/http://philadelphia.cbslocal.com/2014/09/26/health-generic-drugs-prices-increasing/ | archive-date=2016-04-09 | work = CBS Philadelphia | access-date = 2016-03-24 }}</ref> |
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美國紅黴素的價格在2010年至2015年之間上漲三倍，從2010年的每500毫克片劑24美分上漲到2015年的8.96美元。<ref>{{cite web | vauthors = Terry K | date = 2016-09-15 | title = Some Generic Drugs See Huge Price Increases | url = https://www.medscape.com/viewarticle/868812 | website = www.medscape.com | access-date = 2018-06-29 | archive-date = 2017-04-06 | archive-url = https://web.archive.org/web/20170406005414/http://www.medscape.com/viewarticle/868812 | url-status = live }}</ref>2017年，凱薩醫療新聞 (Kaiser Health News) 所進行的一項研究發現在2015年到2016年期間，數十種紅黴素的仿製藥的單位售價漲一倍，甚至有漲到三倍的，而將美國[[聯邦醫療補助]]計劃的支出大幅提高。由於藥物價格上漲，聯邦醫療補助於2016年為紅黴素的支付較2015年的多出2,685,330美元（購買回扣未列入計算）。<ref>{{cite web | vauthors = Lupkin S | work = Kaiser Health News | date = 2017-08-14 | title = Climbing cost of decades-old drugs threatens to break Medicaid bank | url = http://www.philly.com/philly/health/health-cents/climbing-cost-of-decades-old-drugs-threatens-to-break-medicaid-bank-20170814.html | via = The Philadelphia Inquirer | access-date = 2018-06-29 | archive-date = 2018-06-29 | archive-url = https://web.archive.org/web/20180629050058/http://www.philly.com/philly/health/health-cents/climbing-cost-of-decades-old-drugs-threatens-to-break-medicaid-bank-20170814.html | url-status = live }}</ref>到2018年，於美國銷售的紅黴素仿製藥價格又平均上漲5%。<ref>{{cite news |vauthors=Marsh T |title=Are Drugs Really Getting More Expensive? Yes. |url=https://www.goodrx.com/blog/are-drugs-getting-more-expensive/ |website=The GoodRx Prescription Savings Blog |access-date=2018-06-29 |date=2018-02-27 |archive-date=2019-03-23 |archive-url=https://web.archive.org/web/20190323095306/https://www.goodrx.com/blog/are-drugs-getting-more-expensive/ |url-status=live }}</ref> |
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截至2024年月，{{le|英國國家處方集|British National Formulary}}中列出的紅黴素500毫克片劑的價格為36.40英鎊/100片（每片36.4便士）。藥物費用並非由[[國民保健署]]（NHS）的患者支付。[[蘇格蘭]]、[[威爾斯]]和[[北愛爾蘭]]並未為此收取NHS處方費，而在[[英格蘭]]，沒豁免的NHS患者須支付統一的處方費。截至2024年5月，此處方費為每種處方藥9.90英鎊。<ref>{{cite web |
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| title = NHS prescription charges from 1 May 2024 |
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| website = gov.uk |
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| publisher = UK Government |
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| date = 2024-04-05 |
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| url = https://www.gov.uk/government/news/nhs-prescription-charges-from-1-may-2024 |
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| access-date = 2024-08-25 |
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|archive-url=https://web.archive.org/web/20240405105001/https://www.gov.uk/government/news/nhs-prescription-charges-from-1-may-2024 |
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|archive-date=2024-04-05}}</ref> |
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===品牌名稱=== |
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紅黴素的品牌名稱眾多，有Robimycin、E-Mycin、E.E.S.顆粒、E.E.S.-200、E.E.S.-400、E.E.S.-400 Filmtab、Erymax、Ery-Tab、Eryc、Ranbaxy、Erypar、EryPed、Eryped 200、Eryped 400、硬脂酸紅黴素Filmtab、Erythrocot、E-Base、Erythroped、Ilosone、MY -E、Pediamycin、Zineryt、Abboticin、Abboticin-ES、Erycin、PCE Dispertab、Stiemycine、Acnasol和Tiloryth。 |
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==獸醫用途== |
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紅黴素也用於魚類護理 - "廣泛治療和控制細菌性疾病"，如身體黏液、口腔[[真菌]]、[[癤]]病、細菌性[[鰓]]病和出血性[[敗血症]]等。紅黴素在此主要是針對與[[革蘭氏陽性菌]]相關的疾病。<ref>{{cite web|url=https://edis.ifas.ufl.edu/publication/FA084 |title=CIR 84/FA084: Use of Antibiotics in Ornamental Fish Aquaculture|access-date= 2021-09-14|archive-date= 2021-09-11|archive-url=https://web.archive.org/web/20210911175940/https://edis.ifas.ufl.edu/publication/FA084|url-status=live}}</ref> |
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== 參考文獻 == |
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{{Reflist|2}} |
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{{portal bar|Medicine}} |
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{{模板:抗痤瘡製劑}} |
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{{模板:蛋白質合成抑制劑類抗生素}} |
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{{模板:通道阻滯劑}} |
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{{模板:異生素敏感受體調節劑}} |
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{{Portal bar|Medicine}} |
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{{Authority control}} |
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{{draft categories| |
{{draft categories| |
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[[Category:Combination antiviral drugs]] |
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[[分類:叔醇]] |
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[[分類:CYP3A4抑制劑]] |
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[[分類:二甲氨基化合物]] |
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[[分類:醚]] |
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[[分類:肝毒素]] |
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[[分類:內酯]] |
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[[分類:大環內酯類抗生素]] |
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[[[分類:世界衛生組織基本藥物]] |
[[[分類:世界衛生組織基本藥物]] |
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[[分類:RTT]] |
[[分類:RTT]] |
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[[分類:瘧疾]] |
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[[Category:HERG blocker]] |
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[[Category:Drugs developed by Pfizer]] |
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[[Category:Drugs developed by Eli Lilly and Company]] |
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}} |
}} |
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2024年10月29日 (二) 05:18的版本
| 组成 | |
|---|---|
| 青蒿琥酯 | 青蒿素 |
| 美尔奎宁 | 抗疟药 |
| 临床资料 | |
| 给药途径 | 口服给药 |
| ATC码 | |
| 识别信息 | |
| CAS号 | 60473-87-2 |
青蒿琥酯/美尔奎宁（英语：Artesunate/mefloquin）是一种用于治疗疟疾的药物。[1]它是两种抗疟药 - 青蒿琥酯和美尔奎宁组合而成的复方药。[1]建议专用于治疗无并发症的恶性疟原虫导致的疟疾。[2]药物的摄取方式是经由口服。[1]
使用后的副作用与单独使用复方剂中两种成分的相似。[2]使用此复方剂是两种药物具有互补的特点 - 青蒿琥酯可快速杀灭血液中的疟原虫，迅速控制病情，美尔奎宁具有较长的半衰期，可以持续杀灭肝内的疟原虫，减少复发的可能性。此外，复方药可降低治疗时疟原虫可能具某种药物抗药性的问题。此药物也有提供适合儿童的剂型。[2]
青蒿琥酯/美尔奎宁于2008年首次在巴西取得核准用于医疗用途。[3]它已纳入世界卫生组织基本药物标准清单之中。[1]巴西、印度和马来西亚均核准将此药物用于医疗用途，[2]但其并未取得美国食品药物管理局（FDA）的核准，也未在美国贩售。[4]
医疗用途
青蒿琥酯/美尔奎宁种是推荐在东南亚使用的治疗疟疾药物，而如复方药青蒿琥酯/阿莫待奎、蒿甲醚/苯芴醇、青蒿琥酯/磺胺多辛/乙胺嘧啶则通常是在非洲的首选治疗疟疾药物。[5]
特定群体
怀孕
有小型的实验，研究结果并没明确支持青蒿琥酯/美尔奎宁对孕妇安全的证据。孕妇使用此药物应该在医生的密切监控下进行，权衡利弊后做出最适合的治疗方案。目前建议孕妇避免使用含有美尔奎宁的制剂，除非其他药物的治疗无效。[6]
母乳哺育
进行母乳哺育的个体单独使用青蒿琥酯，或是美尔奎宁，对于婴儿看来均无安全问题。[7][8]
禁忌症
对于青蒿琥酯成分严重过敏的个体禁用含有此成分的复方药，[9]于青蒿琥酯给药时应避免同时使用会抑制细胞色素P450家族中CYP2A6的药物（CYP2A6负责代谢多种药物，包括青蒿琥酯。如果服用这类有抑制作用的药物，可能会影响青蒿琥酯在人体的代谢，导致其浓度过高，增加副作用的风险）。前述抑制药物包括胺碘酮、地昔帕明、异烟肼、酮康唑、来曲唑、甲氧沙林 和反苯环丙胺。[10]
而曾有癫痫发作，或是近期有精神障碍的个体禁用含有美尔奎宁的制剂。[11]
交互作用
根据一项小型研究，证明青蒿素和美尔奎宁之间的药物交互作用并不严重。[12]
药物开发历史
此复方剂由非营利性药物研究和开发组织被忽视疾病药物倡议（DNDi）开发。[13]
传统上药物通常经由制药公司自行研发，研究和开发成本最终通过药物销售来回收。开发用于治疗被忽视的热带疾病的药物不能只考虑市场的获利，需要一种超越市场驱动的研究和开发思维。[13]
DNDi于全球各大洲建立起合作伙伴关系，将配方、控制和生产到临床试验以及产品注册的问题全部解决，开发出此种安全有效的组合治疗药物，以供应供资源匮乏地区的患者使用。而药物制造从巴西的Farmanguinhos/Fiocruz（Institute of Pharmaceutical Technology）技术移转到印度的跨国制药与生技公司西普拉制药，更是创下发展中国家间的首例。通过这样的合作，发展中国家在知识和技术方面得以互补，共同提升整体能力。。[13]
青蒿素和美尔奎宁这两种药物对治疗无并发症恶性疟原虫导致的疟疾已有长时间的经验，也有良好的安全性。把这两种药结合，以固定剂量的复方形式给药，可让病人更易按时服药，同时也能减少疟原虫产生抗药性的风险。[13]
参见
参考文献
- ^ 1.0 1.1 1.2 1.3 World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771
. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ 2.0 2.1 2.2 2.3 World Health Organization. The Selection and Use of Essential Medicines: Report of the WHO Expert Committee, 2013 (including the 18th WHO Model List of Essential Medicines and the 4th WHO Model List of Essential Medicines for Children). World Health Organization. 2014: 43–4. ISBN 9789241209854. hdl:10665/112729 .
- ^ Staines HM, Krishna S. Treatment and Prevention of Malaria: Antimalarial Drug Chemistry, Action and Use. Springer Science & Business Media. 2012: 239. ISBN 9783034604802. （原始内容存档于2016-12-20） （英语）.
- ^ Sanford CA, Jong EC, Pottinger PS. The Travel and Tropical Medicine Manual 5. Elsevier Health Sciences. 2016: 307. ISBN 9780323417426. （原始内容存档于2016-12-20） （英语）.
- ^ Marcondes CB. Arthropod Borne Diseases. Springer. 2016: 35. ISBN 9783319138848. （原始内容存档于2016-12-20） （英语）.
- ^ Valea, Innocent; Tinto, Halidou. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso. Journal of Antimicrobial Chemotherapy. 2014-06-02, 69 (9): 2499–2507 [2024-10-19]. doi:10.1093/jac/dku154.
- ^ Artesunate use while Breastfeeding | Drugs.com. www.drugs.com. [2016-12-07]. （原始内容存档于2016-12-20）.
- ^ Mefloquine (PDF). Medicines for the Prevention of Malaria While Traveling. Atlanta, Georgia: Centers for Disease Control and Prevention. 2019 [2019-03-30].
- ^ Hess KM, Goad JA, Arguin PM. Intravenous artesunate for the treatment of severe malaria. The Annals of Pharmacotherapy. 1 January 2010, 44 (7–8): 1250–1258. PMID 20551300. S2CID 23946665. doi:10.1345/aph.1M732. （原始内容存档于10 November 2016）.
- ^ Artesunate Amodiaquine Winthrop (artesunate, amodiaquine) [summary of product characteristics] (PDF). Sanofi-Aventis. （原始内容存档 (PDF)于2016-10-24）.
- ^ Lariam. The American Society of Health-System Pharmacists. [2011-04-03]. （原始内容存档于2012-01-07）.
- ^ Lefèvre, Gilbert; Bindschedler, Margaretha. Pharmacokinetic interaction trial between co-artemether and mefloquine. European Journal of Pharmaceutical Sciences. April 2000, 10 (2): 141–151 [2024-10-19]. doi:10.1016/S0928-0987(00)00060-9.
- ^ 13.0 13.1 13.2 13.3 Wells, Susan; Diap, Graciela. The story of artesunate-mefloquine (ASMQ), innovative partnerships in drug development: case study. Malaria Journal. 2013-02-21 [2024-10-19]. doi:10.1186/1475-2875-12-68.
外部链接
- Artesunate mixture with mefloquine. Drug Information Portal. U.S. National Library of Medicine.
