Friedland Gerald, Andrews Laurie, Schreibman Tanya, Agarwala Sangeeta, Daley Leith, Child Michael, Shi Julia, Wang Yonghua, O'Mara Edward
AIDS Program, Yale School of Medicine, New Haven, Connecticut 06510, USA.
AIDS. 2005 Oct 14;19(15):1635-41. doi: 10.1097/01.aids.0000183628.20041.f2.
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.
To determine if atazanavir, a once-daily protease inhibitor and moderate inhibitor of P450 CYP3A4, exhibited pharmacokinetic interactions with (R)-methadone.
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.
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 (CI), 0.95-1.10] for the area under the concentration-time curve (AUC), 0.91 (90% CI, 0.84-1.00) for plasma maximal concentration and 1.11 (90% CI, 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.
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.
对感染HIV的阿片类药物成瘾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，常用美沙酮。抗逆转录病毒药物与美沙酮之间的药理相互作用可能导致阿片类药物戒断或副作用增加。
确定每日一次的蛋白酶抑制剂阿扎那韦（一种P450 CYP3A4中度抑制剂）是否与（R）-美沙酮存在药代动力学相互作用。
在16例接受慢性美沙酮治疗的患者中，于每日服用阿扎那韦14天之前和之后测量美沙酮的药代动力学参数。美沙酮总异构体、（R）-（活性）异构体和（S）-（非活性）异构体的稳态药代动力学值源自血浆浓度与时间的数据。监测阿片类药物戒断和过量的症状。
对于活性异构体（R）-美沙酮，与阿扎那韦合用相对于单独使用美沙酮时，浓度-时间曲线下面积（AUC）的几何均值比为1.03 [90%置信区间（CI），0.95 - 1.10]，血浆最大浓度为0.91（90%CI，0.84 - 1.00），血浆谷浓度为1.11（90%CI，1.02 - 1.20）。这三个值的置信区间均在（R）-美沙酮无效应或生物等效性范围0.80 - 1.25之内。在与阿扎那韦合用时，非活性（S）-美沙酮略有降低。未检测到阿片类药物戒断或过量的临床相关症状。阿扎那韦的暴露量在先前报告的值范围内。
未发现阿扎那韦与美沙酮之间存在临床相关的药代动力学相互作用。对于同时接受阿片类药物滥用治疗和HIV疾病治疗的患者，当联合使用美沙酮和阿扎那韦时，无需推荐调整剂量。
