Lack of an effect of atazanavir on steady-state pharmacokineties of methadone in patients chronically treated for opiate addiction
Lack of an effect of atazanavir on steady-state pharmacokineties of methadone in patients chronically treated for opiate addiction
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DOI：
10.1097/01.aids.0000183628.20041.f2
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发表时间：
2005-10-14
期刊：
影响因子：
3.8
通讯作者：
O'Mara, E
中科院分区：
文献类型：
--
作者：
Friedland, G;Andrews, L;O'Mara, E
背景：对感染艾滋病毒的鸦片成瘾吸毒者进行有效的抗逆转录病毒治疗通常需要同时进行药物滥用治疗，通常是美沙酮。抗逆转录病毒药物与美沙酮之间的药理学相互作用可能导致阿片戒断或增加副作用。 目的： 确定阿扎那韦（一种每日一次的蛋白酶抑制剂和 P450 CYP3A4 的中度抑制剂）是否与 (R)-美沙酮表现出药代动力学相互作用。 方法： 在 16 名接受长期美沙酮治疗的患者每天服用阿扎那韦 14 天之前和之后测量美沙酮的药代动力学参数。阿扎那韦。美沙酮总异构体（R）-（活性）和（S）-（非活性）的稳态药代动力学值源自血浆浓度与时间数据。监测阿片戒断和过量症状。 结果：对于活性异构体 (R)-美沙酮，与阿扎那韦联合用药相对于单独美沙酮的几何平均值之比，浓度-时间曲线下面积 (AUC) 为 1.03 [90% 置信区间 (Cl), 0.95-1.10]，血浆为 0.91 (90% Cl, 0.84-1.00)最大浓度和血浆谷浓度为 1.11 (90% Cl, 1.02-1.20)。对于 (R)-美沙酮，所有三种药物的置信区间均在 0.80-1.25 的无作用或生物等效性范围内。在阿扎那韦联合用药期间，非活性（S）-美沙酮略有减少。未检测到阿片戒断或过量的临床相关症状。阿扎那韦的暴露量在之前报道的值范围内。结论：阿扎那韦和美沙酮之间没有发现临床相关的药代动力学相互作用。当美沙酮或阿扎那韦同时用于阿片类药物滥用和艾滋病毒治疗的患者时，无需建议调整剂量。 (c) 2005 年利平科特·威廉姆斯·威尔金斯
Background: Effective antiretroviral treatment of opiate-addicted drug users with HIV infection often requires concomitant substance abuse treatment, commonly with methadone. Pharmacological interactions between antiretroviral drugs and methadone may result in opiate withdrawal or increased side effects.Objectives: To determine if atazanavir, a once-daily protease inhibitor and moderate inhibitor of P450 CYP3A4, exhibited pharmacokinetic interactions with (R)-methadone.Methods: Methadone pharmacokinetic parameters were measured in 16 patients on chronic methadone therapy prior to and after 14 days of daily administration of atazanavir. Steady-state pharmacokinetic values for total, (R)-(active) and (S)- (inactive) isomers of methadone were derived from plasma concentrations versus time data. Symptoms of opiate withdrawal and excess were monitored.Results: For the active isomer (R)-methadone, the ratio of geometric means for coadministration with atazanavir relative to methadone alone were 1.03 [90% confidence interval (Cl), 0.95-1.10] for the area under the concentration-time curve (AUC), 0.91 (90% Cl, 0.84-1.00) for plasma maximal concentration and 1.11 (90% Cl, 1.02-1.20) for plasma trough concentration. Confidence intervals for all three were within the no-effect or bioequivalence range of 0.80-1.25 for (R)-methadone. Inactive (S)-methadone was modestly reduced during atazanavir coadministration. Clinically relevant symptoms of opiate withdrawal or excess were not detected. Exposures to atazanavir were within range of previously reported values.Conclusions: No clinically relevant pharmacokinetic interactions were found between atazanavir and methadone. Dosage adjustment need not be recommended for either methadone or atazanavir when co-administered to patients treated for opiate abuse and HIV disease. (c) 2005 Lippincott Williams & Wilkins