An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome p450 3A4 inhibitor ritonavir
An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome p450 3A4 inhibitor ritonavir
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DOI：
10.1016/s0149-2918(03)80076-0
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发表时间：
2003-04-01
影响因子：
3.2
通讯作者：
Abramowitz, W
中科院分区：
文献类型：
--
作者：
Gutierrez, MM;Rosenberg, J;Abramowitz, W
背景：抑郁症通常与多种疾病并存，诊断为抑郁症的患者通常接受多种药物治疗。因此，希望避免在这些患者中共同施用具有药物相互作用潜力的药剂。虽然艾司西酞普兰及其代谢产物对细胞色素P450（P450）3A 4同工酶的抑制作用微弱到可以忽略，因此不太可能影响利托那韦的血浆浓度（一种CYP 3A 4底物和原型CYP 3A 4抑制剂），利托那韦可能会影响艾司西酞普兰的血浆浓度，因为CYP 3A 4部分负责艾司西酞普兰转化为其主要代谢产物，S-去甲基西酞普兰（S-DCT）。目的：本研究的目的是调查健康年轻受试者中同时给予单剂量艾司西酞普兰和利托那韦后，两者之间药代动力学相互作用的可能性。方法：在本单中心、随机、开放标签、3向交叉研究中，受试者接受以下各项：艾司西酞普兰20 mg单次给药、利托那韦600 mg单次给药以及艾司西酞普兰20 mg和利托那韦600 mg单次给药。采集血液并分析血浆的药代动力学参数（最大血药浓度[C-max]、至C-max的时间[T-max]、血药浓度-时间曲线下面积、血浆消除半衰期、口服清除率和表观分布容积）。（男11人，女10人;平均[SD]年龄，28.4 [4.4]岁），18人完成了研究。在艾司西酞普兰和利托那韦同时给药后，除了表观分布容积外，降低约10%（P < 0.001）。S-DCT的药代动力学不受利托那韦联合给药的影响，但Tmax除外，在利托那韦存在的情况下，Tmax增加。利托那韦的药代动力学参数也不受共同管理的艾司西酞普兰。结论：在一般情况下，没有药代动力学之间的相互作用观察艾司西酞普兰和利托那韦在本研究中。版权所有（C）2003 Excerpta Medica，Inc.
Background: Depression often coexists with a number of disease states, and patients with a diagnosis of depression often receive multiple medications. Thus, it is desirable to avoid coadministration of agents that have a potential for drug interactions in these patients. Although escitalopram and its metabolites are weak to negligible inhibitors of the cytochrome P450 (CYP) 3A4 isozyme and are therefore unlikely to affect plasma concentrations of ritonavir (a CYP3A4 substrate and prototype CYP3A4 inhibitor), ritonavir may potentially affect plasma concentrations of escitalopram, as CYP3A4 is partially responsible for conversion of escitalopram to its major metabolite, S-demethylcitalopram (S-DCT).Objective: The aim of this study was to investigate the potential for pharmacokinetic interaction between escitalopram and ritonavir after concomitant administration of a single dose of each in healthy young subjects.Methods: in this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of escitalopram 20 mg, a single dose of ritonavir 600 mg, and single doses of both escitalopram 20 mg and ritonavir 600 mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration [C-max], time to C-max [T-max], area under the plasma concentration-time curve, plasma elimination half-life, oral clearance, and apparent volume of distribution) of escitalopram, S-DCT, and ritonavir.Results: Of 21 subjects (11 men, 10 women; mean [SD] age, 28.4 [4.4] years) who were enrolled, 18 completed the study After concomitant administration of escitalopram and ritonavir, no statistically significant differences were noted in the pharmacokinetics of escitalopram, with the exception of apparent volume of distribution, which was reduced by similar to10% (P < 0.001). The pharmacokinetics of S-DCT were unaffected by coadministration of ritonavir, with the exception of T-max, which was increased in the presence of ritonavir. The pharmacokinetic parameters of ritonavir were also unaffected by coadministration of escitalopram.Conclusion: In general, no pharmacokinetic interaction was observed between escitalopram and ritonavir in the present study. Copyright (C) 2003 Excerpta Medica, Inc.