Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers

被引：16

作者：

Sekar V.J. ^{[1
]}

Lefebvre E. ^{[1
]}

De Marez T. ^{[1
]}

Spinosa-Guzman S. ^{[2
]}

De Pauw M. ^{[2
]}

De Paepe E. ^{[2
]}

Vangeneugden T. ^{[2
]}

Hoetelmans R.M.W. ^{[2
]}

机构：

[1] Tibotec Inc., Yardley, PA

[2] Tibotec BVBA, Mechelen

来源：

Drugs in R & D | 2007年 / 8卷 / 4期

关键词：

Ritonavir; Systemic Exposure; Atazanavir; Amprenavir; Darunavir;

D O I：

10.2165/00126839-200708040-00004

中图分类号：

学科分类号：

摘要：

Background and objective: To investigate the potential for pharmacokinetic interactions between the protease inhibitors darunavir (DRV, TMC114) coadministered with low-dose ritonavir (darunavir/r), and atazanavir in HIV-negative, healthy volunteers. Methods: This was an open-label, randomised, three-period, crossover study. Darunavir/r (400/100mg twice daily), atazanavir/r (300/100mg once daily) or darunavir/r (400/100mg twice daily) plus atazanavir (300mg once daily) were administered in three separate sessions, with a washout period of at least 7 days between regimens. The follow-up lasted 30 days. Twenty-three healthy volunteers participated. Pharmacokinetic assessments were performed at steady-state on day 7. Plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were compared between treatments. The safety and tolerability of the study medications were monitored throughout. Results: Darunavir pharmacokinetics were unaffected by atazanavir. No change in overall exposure to atazanavir was observed during coadministration with darunavir/r. However, there was a 52% increase in minimum atazanavir plasma concentration (least squares mean ratio [90% CI 0.99, 2.34]). Mean systemic exposure to ritonavir was increased by 65% and 106%, respectively, with the combination treatment compared with darunavir/r alone or atazanavir/r alone. There were no apparent differences in mean changes in lipids between the darunavir/r, atazanavir/r or darunavir/r plus atazanavir regimens. Hyperbilirubinaemia and ocular icterus were reported with atazanavir-containing regimens. Conclusion: Atazanavir at a dose of 300mg once daily can be coadministered with a darunavir/r twice-daily regimen without any dose adjustment if there is a clinical need to combine darunavir/r and atazanavir in HIV-1-infected patients. © 2007 Adis Data Information BV. All rights reserved.

引用

页码：241 / 248

页数：7

共 21 条

[1]

De Meyer S., Azijn H., Surleraux D., Et al., TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates, Antimicrob Agents Chemother, 49, pp. 2314-2321, (2005)

[2]

Katlama C., Esposito R., Gatell J., Et al., Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1, AIDS, 21, pp. 395-402, (2007)

[3]

Haubrich R., Berger D., Chiliade P., Et al., Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: POWER 2, AIDS, 21, 6, (2007)

[4]

Molina J.M., Cohen C., Katlama C., Et al., POWER 3: 24-week efficacy and safety results of TMC114/r in treatment-experienced patients [abstract P4], HIV Med, 7, SUPPL. 1, (2006)

[5]

Prezista® (darunavir) prescribing information

[6]

Sekar V., Spinosa-Guzman S., Lefebvre E., Et al., Clinical Pharmacology of TMC114: A potent HIV protease inhibitor, 16th International AIDS Conference, (2006)

[7]

Reyataz® (atazanavir sulfate) prescribing information, (2006)

[8]

Staszewski S., Babacan E., Stephan C., Et al., The LOPSAQ study: 48 week analysis of a boosted double protease inhibitor regimen containing lopinavir/ritonavir plus saquinavir without additional antiretroviral therapy, J Antimicrob Chemother, 58, 5, pp. 1024-1030, (2006)

[9]

Ribera E., Azuaje C., Lopez R.M., Et al., Atazanavir and lopinavir/ ritonavir: Pharmacokinetics, safety and efficacy of a promising double-boosted protease inhibitor regimen, AIDS, 20, 8, pp. 1131-1139, (2006)

[10]

Koch G., The use of nonparametric methods in the statistical analysis of the two-period change-over design, Biometrics, 28, pp. 577-584, (1972)

← 1 2 3 →