Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen

被引:63
|
作者
Boffito, M
Kurowski, M
Kruse, G
Hill, A
Benzie, AA
Nelson, MR
Moyle, GJ
Gazzard, BG
Pozniak, AL
机构
[1] Chelsea & Westminster Hosp, PK Res Ltd, St Stephens Ctr, London SW10 9NH, England
[2] Therapia GmbH, Berlin, Germany
[3] Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England
关键词
atazanavir; drug-drug interaction; once-daily; pharmacokinetics; ritonavir; saquinavir;
D O I
10.1097/00002030-200406180-00007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To determine the pharmacokinetics of saquinavir hard-gel capsules/ ritonavir/atazanavir co-administered once daily at 1600/100/300 mg in HIV-infected individuals. Methods: Eighteen patients receiving saquinavir/ritonavir switched to 1600/100 mg once daily a minimum of 3 days before the study. On study day 1, levels of saquinavir and ritonavir were determined over 24 h. Atazanavir (300 mg once daily) was then added to the regimen. On day 11, a pharmacokinetic analysis was performed. Atazanavir was discontinued on day 32. Drug concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR) and 95% confidence intervals (CI) were used to compare saquinavir and ritonavir pharmacokinetic parameters, with and without atazanavir. A safety analysis was performed at screening, days 1, 11, 32 and follow-up. Results: After the addition of atazanavir, statistically significant increases in saquinavir trough plasma concentration (C-trough GMR, 95% CI 2.12, 1.72-3.50), maximum plasma concentration (C-max 1.42, 1.24-1.94), area under the plasma concentration-time curve from 0-24 h (AUC(0-24) 1.60, 1.35-2.43) and ritonavir C-max (1.58, 1.32-2.08), AUC(0-24) (1.41, 1.22-1.74) were observed. The pharmacokinetics of atazanavir compared with those obtained in patients receiving atazanavir/ritonavir without saquinavir. Four patients developed scleral icterus and two jaundice. Total and unconjugated bilirubin increased approximately fivefold during atazanavir therapy. Conclusion: The addition of atazanavir to saquinavir/ritonavir increased saquinavir C-trough, C-max and AUC(0-24) by 112, 42 and 60%. Ritonavir C-max, and AUC(0-24) increased by 34 and 41%. The regimen was well tolerated, with no significant change in laboratory parameters, except for the occurrence of hyperbilirubinemia. (C) 2004 Lippincott Williams Wilkins.
引用
收藏
页码:1291 / 1297
页数:7
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