阿巴卡韦在未感染和感染人类免疫缺陷病毒（HIV）的患者中，分别在不存在和存在阿扎那韦/利托那韦或洛匹那韦/利托那韦的情况下的血浆药代动力学，反之亦然。

Abacavir plasma pharmacokinetics in the absence and presence of atazanavir/ritonavir or lopinavir/ritonavir and vice versa in HIV-infected patients.

作者信息

Waters Lauro J, Moyle Graeme, Bonora Stefano, D'Avolio Antonio, Else Laura, Mandalia Sundhiya, Pozniak Anton, Nelson Mark, Gazzard Brian, Back David, Boffito Marta

机构信息

St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK.

出版信息

Antivir Ther. 2007;12(5):825-30.

PMID:17713166

Abstract

BACKGROUND

Significant interactions between abacavir and other antiretrovirals have not been reported. This study investigated the steady-state plasma pharmacokinetics of abacavir when co-administered with atazanavir/ritonavir or lopinavir/ritonavir in HIV-infected individuals.

METHODS

HIV-infected subjects on abacavir (600 mg once daily) plus two nucleoside reverse transcriptase inhibitors (NRTIs) (excluding tenofovir) underwent a 24 h pharmacokinetic assessment for plasma abacavir concentrations. Atazanavir/ritonavir (300/100 mg once daily; arm (1) or lopinavir/ritonavir (400/100 mg twice daily; arm (2) were then added and the 24 h pharmacokinetic assessment repeated. Arm 3 included subjects stable on atazanavir/ritonavir or lopinavir/ritonavir and two NRTIs (excluding tenofovir or abacavir). These patients underwent a pharmacokinetic assessment for atazanavir/ritonavir or lopinavir/ritonavir concentrations on day 1, abacavir (600 mg once daily) was then added to the regimen and the pharmacokinetic assessment repeated. Within-subject changes in drug exposure were evaluated by geometric mean (GM) ratios and 95% confidence intervals (CI).

RESULTS

Twenty-four patients completed the study. GM (95% CI) abacavir area under the curve (AUC) was 18,621 (15,900-21,807) and 15,136 (13,339-17,174) ng.h/ml without and with atazanavir/ritonavir and 15,136 (12,298-18,628) and 10,471 (9,270-11,828) ng.h/ml without and with lopinavir/ritonavir. GM (95% CI) atazanavir AUC without and with abacavir was 26,915 (13,252-54,666) and 28,840 (19,213-43,291) ng.h/ml; lopinavir AUC without and with abacavir was 60,253 (48,084-75,509) and 63,096 (48,128-82,718) ng.h/ml.

CONCLUSIONS

No changes in atazanavir or lopinavir exposures were observed following the addition of abacavir; however, decreases in abacavir plasma exposure of 17% and 32% were observed following the addition of atazanavir/ritonavir or lopinavir/ritonavir, respectively.

摘要

背景

尚未有关于阿巴卡韦与其他抗逆转录病毒药物之间显著相互作用的报道。本研究调查了在HIV感染个体中，阿巴卡韦与阿扎那韦/利托那韦或洛匹那韦/利托那韦合用时的稳态血浆药代动力学。

方法

正在接受阿巴卡韦（每日一次，600毫克）加两种核苷类逆转录酶抑制剂（NRTIs）（不包括替诺福韦）治疗的HIV感染受试者，接受了24小时血浆阿巴卡韦浓度的药代动力学评估。随后添加阿扎那韦/利托那韦（每日一次，300/100毫克；第1组）或洛匹那韦/利托那韦（每日两次，400/100毫克；第2组），并重复24小时药代动力学评估。第3组包括在阿扎那韦/利托那韦或洛匹那韦/利托那韦及两种NRTIs（不包括替诺福韦或阿巴卡韦）治疗下病情稳定的受试者。这些患者在第1天接受了阿扎那韦/利托那韦或洛匹那韦/利托那韦浓度的药代动力学评估，随后在治疗方案中添加阿巴卡韦（每日一次，600毫克）并重复药代动力学评估。通过几何均值（GM）比值和95%置信区间（CI）评估药物暴露的个体内变化。

结果

24名患者完成了研究。在未使用和使用阿扎那韦/利托那韦的情况下阿巴卡韦曲线下面积（AUC）的GM（95%CI）分别为18,621（15,900 - 21,807）和15,136（13,339 - 17,174）纳克·时/毫升；在未使用和使用洛匹那韦/利托那韦的情况下分别为15,136（12,298 - 1,8628）和10,471（9,270 - 11,828）纳克·时/毫升。在未使用和使用阿巴卡韦的情况下阿扎那韦AUC的GM（95%CI）分别为26,915（13,252 -

54,666）和28,840（19,213 - 43,291）纳克·时/毫升；在未使用和使用阿巴卡韦的情况下洛匹那韦AUC分别为60,253（48,084 - 75,509）和63,096（48,12