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新型抗偏头痛化合物佐米曲普坦(佐米格,311C90)可能存在的药物相互作用。

Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig, 311C90).

作者信息

Rolan P

机构信息

Department of Neurology, Manchester Royal Infirmary, Manchester, UK.

出版信息

Cephalalgia. 1997 Oct;17 Suppl 18:21-7. doi: 10.1177/0333102497017S1804.

DOI:10.1177/0333102497017S1804
PMID:9399014
Abstract

Seven randomized studies in healthy volunteers have investigated interactions between zolmitriptan (Zomig, formerly 311C90), a 5HT1B/1D agonist for acute migraine therapy, and selected drugs with which there was a possibility of interaction or a likelihood of concurrent use. Co-administration of oral dihydroergotamine, ergotamine, pizotifen, fluoxetine, paracetamol (acetaminophen)/metoclopramide or selegiline had no clinically significant effects on the pharmacokinetics of zolmitriptan or its metabolites, although small changes were observed in some cases. Co-administration of propranolol resulted in a 56% increase in the area under the plasma concentration-time curve (AUC) of zolmitriptan and a 11% decrease in the AUC of the active metabolite 183C91. However, these pharmacokinetic changes are unlikely to be relevant at lower clinical doses. Moclobemide, a monoamine oxidase A (MAO-A) inhibitor, decreased the clearance of zolmitriptan and, in particular, 183C91. This suggests that MAO-A is involved in the metabolism of 183C91 and it may be prudent to limit the daily zolmitriptan dose in migraine patients maintained on a MAO-A inhibitor. The clinically insignificant blood pressure increases produced by zolmitriptan, and the tolerability profile of this agent, were unaffected by any of the concomitant medications. Clinically significant interactions between zolmitriptan and commonly co-prescribed antimigraine therapies are unlikely.

摘要

七项针对健康志愿者的随机研究调查了用于急性偏头痛治疗的5HT1B/1D激动剂佐米曲普坦(佐米格,原311C90)与某些可能存在相互作用或有同时使用可能性的药物之间的相互作用。口服二氢麦角胺、麦角胺、苯噻啶、氟西汀、对乙酰氨基酚/甲氧氯普胺或司来吉兰的联合使用对佐米曲普坦及其代谢物的药代动力学没有临床显著影响,尽管在某些情况下观察到了微小变化。普萘洛尔的联合使用导致佐米曲普坦的血浆浓度-时间曲线下面积(AUC)增加56%,活性代谢物183C91的AUC降低11%。然而,在较低临床剂量下,这些药代动力学变化可能无关紧要。单胺氧化酶A(MAO-A)抑制剂吗氯贝胺降低了佐米曲普坦尤其是183C91的清除率。这表明MAO-A参与了183C91的代谢,对于正在服用MAO-A抑制剂的偏头痛患者,限制佐米曲普坦的每日剂量可能是谨慎的做法。佐米曲普坦引起的临床上无显著意义的血压升高以及该药物的耐受性不受任何伴随药物的影响。佐米曲普坦与常用的联合开具的抗偏头痛疗法之间不太可能发生具有临床意义的相互作用。

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