奈韦拉平对接受阿扎那韦/利托那韦治疗的 HIV 感染患者的阿扎那韦稳态谷浓度的影响。

Effect of nevirapine on the steady-state trough concentrations of atazanavir in HIV-infected patients receiving atazanavir/ritonavir.

机构信息

Lluita contra la Sida Foundation, HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

出版信息

Ther Drug Monit. 2010 Feb;32(1):93-6. doi: 10.1097/FTD.0b013e3181cb479f.

DOI:10.1097/FTD.0b013e3181cb479f

PMID:20040897

Abstract

MATERIAL AND METHODS

To evaluate the influence of nevirapine on atazanavir trough concentrations (Ctrough) in a group of HIV-infected patients, we performed an open-label pilot study enrolling patients receiving 300/100 mg atazanavir/ritonavir once daily for 2 weeks or longer. Nevirapine was added at a dose of 200 mg once daily from Days 0 to 14 and 200 mg twice daily from Days 14 to 28. Atazanavir and nevirapine plasma Ctroughs were determined at Days 0 and 28. Atazanavir Ctroughs were compared between Days 0 and 28. Atazanavir and nevirapine Ctroughs at Day 28 were compared with historical controls receiving either 400 mg atazanavir once daily or 200 mg nevirapine twice daily.

RESULTS

Fourteen patients were enrolled and 11 completed the study. The geometric mean (range) atazanavir Ctrough decreased from 0.631 mg/L (range, 0.235-1.87 mg/L) at Day 0 to 0.316 mg/L (range, 0.142-1.109 mg/L) at Day 28 to give a geometric mean ratio of 0.59 (95% confidence interval, 0.38-0.80; P = 0.026); nonetheless, the atazanavir Ctrough remained higher than the minimum effective concentration in 80% of the participants and higher than the median concentration in the control subjects receiving 400 mg atazanavir once daily without ritonavir (geometric mean ratio, 3.20; 95% confidence interval, 1.65-6.22; P = 0.001). The nevirapine Ctrough at Day 28 was slightly higher than in the historical controls on 200 mg nevirapine twice daily without atazanavir (geometric mean ratio, 1.46; 95% confidence interval, 1.04-2.06; P = 0.030).

CONCLUSION

We conclude that coadministration of 300/100 mg atazanavir/ritonavir once daily plus 200 mg nevirapine twice daily was safe and well tolerated but resulted in a decrease of atazanavir Ctrough by nearly half. Therefore, monitoring atazanavir Ctrough is recommended in patients treated with this drug combination, and increasing the atazanavir dose might be necessary.

摘要

材料和方法

为了评估奈韦拉平对一组接受每日一次 300/100 毫克阿扎那韦/利托那韦治疗达 2 周或更长时间的 HIV 感染患者的阿扎那韦谷浓度（Ctrough）的影响，我们进行了一项开放标签的试点研究。奈韦拉平的剂量为 200 毫克，每日一次，从第 0 天到第 14 天，从第 14 天到第 28 天，每日两次。在第 0 天和第 28 天测定阿扎那韦和奈韦拉平的血浆 Ctrough。比较第 0 天和第 28 天的阿扎那韦 Ctrough。第 28 天的阿扎那韦和奈韦拉平 Ctrough 与接受每日一次 400 毫克阿扎那韦或每日两次 200 毫克奈韦拉平治疗的历史对照进行比较。

结果

共纳入 14 例患者，11 例完成研究。阿扎那韦 Ctrough 的几何平均值（范围）从第 0 天的 0.631 毫克/升（范围，0.235-1.87 毫克/升）降至第 28 天的 0.316 毫克/升（范围，0.142-1.109 毫克/升），几何平均值比为 0.59（95%置信区间，0.38-0.80；P = 0.026）；然而，80%的参与者的阿扎那韦 Ctrough 仍高于最低有效浓度，高于接受无利托那韦的每日一次 400 毫克阿扎那韦的对照组的中位数浓度（几何平均值比，3.20；95%置信区间，1.65-6.22；P = 0.001）。第 28 天的奈韦拉平 Ctrough 略高于历史对照中无阿扎那韦的每日两次 200 毫克奈韦拉平（几何平均值比，1.46；95%置信区间，1.04-2.06；P = 0.030）。