Pharmacokinetics of Darunavir/Ritonavir and TMC125 alone and Coadministered in HIV-Negative Volunteers
| Autor: | Brian Woodfall, Vanitha Sekar, Goedele De Smedt, Richard M. W. Hoetelmans, Monika Schöller-Gyüre, Thomas N. Kakuda, Eric Lefebvre, Monika Peeters |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Darunavir+Ritonavir Human immunodeficiency virus (HIV) Etravirine Pharmacology medicine.disease_cause Drug Administration Schedule Pharmacokinetics Reference Values Nitriles medicine Humans Drug Interactions Pharmacology (medical) Protease inhibitor (pharmacology) Darunavir Sulfonamides Cross-Over Studies Ritonavir business.industry HIV Protease Inhibitors Middle Aged Pyridazines Drug Combinations Pyrimidines Infectious Diseases Reverse Transcriptase Inhibitors Drug Therapy Combination Female business medicine.drug |
| Zdroj: | Antiviral Therapy. 12:789-796 |
| ISSN: | 2040-2058 1359-6535 |
| Popis: | ObjectiveTo evaluate the pharmacokinetics of TMC125 (etravirine) and darunavir (DRV) with low-dose ritonavir (DRV/r).DesignOpen-label, randomized, two-way crossover Phase I trial.MethodsThirty-two HIV-negative volunteers were randomized 1:1 to two panels. All received TMC125 100 mg twice daily for 8 days and, after 14 days washout, DRV/r 600/100 mg twice daily for 16 days. During days 9–16, TMC125 100 or 200 mg twice daily was coadministered (Panel I or II, respectively).ResultsTwenty-three volunteers completed the trial. With DRV/r coadministration, mean exposure (area under the plasma concentration-time curve from 0 to 12 h [AUC12h]) to TMC125 given as 100 mg twice daily was decreased by 37%; maximum and minimum plasma concentrations (Cmaxand Cmin) were decreased by 32% and 49%, respectively. For TMC125 200 mg twice daily coadministered with DRV/r, AUC12h, Cmaxand Cminof TMC125 were 80%, 81% and 67% greater, respectively, versus TMC125 100mg twice daily alone. DRV pharmacokinetics were unchanged except a 15% increase in AUC12hwhen given with TMC125 200 mg twice daily.ConclusionsNo clinically relevant changes in DRV pharmacokinetics were observed when combined with TMC125; therefore DRV dose adjustment is not required. Coadministration of TMC125 100 mg twice daily with DRV/r decreased TMC125 exposure by 37%. The increase of TMC125 exposure by 80% when given as 200 mg twice daily reflects the higher dose and the interaction with DRV/r. The magnitude of this interaction is comparable to TMC125 interactions with other boosted PIs observed in Phase IIb trials in HIV-1-infected patients. As these trials demonstrated TMC125 efficacy, no dose adjustment of TMC125 is needed when combined with DRV/r. |
| Databáze: | OpenAIRE |
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