Contact us to report problems with: For Publishers For Researchers For Librarians EFFECT OF REPEATED DOSES OF DARUNAVIR PLUS LOW-DOSE RITONAVIR ON THE PHARMACOKINETICS OF SILDENAFIL IN HEALTHY MALE SUBJECTS: PHASE I RANDOMIZED, OPEN-LABEL, TWO-WAY CROSSOVER STUDY AUTHORS: Sekar, V.E.Marez, T.Pauw, M.Paepe, E.T.R. SOURCE: , Volume 28, Number 8, 2008 , pp.PUBLISHER: Key: - Free Content - New Content - Subscribed Content - Free Trial Content ABSTRACT: BACKGROUND AND OBJECTIVES: Darunavir (DRV, TMC114) is a novel protease inhibitor administered inbination with low-dose ritonavir (DRV/r) and is highly active against both wild-type and multidrug-resistant HIV-1 strains.Is an oral therapy for erectile dysfunction.Of protease inhibitors and sildenafil increases sildenafil plasma concentrations.Potential for a pharmacokinetic drug interaction exists when sildenafil and DRV/r are co-administered, as these drugs are primarily metabolized by cytochrome P450 (CYP) 3A, and darunavir and ritonavir are CYP3A inhibitors.Primary objective of this open-label, crossover, phase I study was to assess the effect of multiple doses of DRV/r on the pharmacokinetics of sildenafil and its active metabolite _N_-desmethyl sildenafil.Secondary objective was to assess the short-term safety and tolerability of co-administration of sildenafil and DRV/r.HIV-negative healthy male subjects were randomized to one of two sequences.Two sessions each subject received treatments A and B.Treatment A, a single dose of sildenafil 100 mg was administered.Treatment B, the subjects received DRV/r 400/100 mg twice daily for 8 days and on day 7 a single dose of sildenafil 25 mg was co-administered.Pharmacokinetic profiles of sildenafil, _N_-desmethyl sildenafil, darunavir and ritonavir were determined.Tolerability were also assessed.Exposure (area under the plasma concentration-time curve ) values decreased by approximately 95% when sildenafil 25 mg was co-administered with DRV/rpared with sildenafil 100 mg alone.With DRV/r and sildenafil was generally safe and well tolerated.Exposure is increased in the presence of DRV/r.Setting, a dose adjustment for sildenafil is warranted; no more than 25 mg of sildenafil is rmended over a 48-hour period when co-administered with DRV/r.KEYWORDS: ; ; ; ; ; DOCUMENT TYPE: Research article AFFILIATIONS: 1: 1 Tibotec Inc.Pennsylvania, USA 2: 2 Janssen-Cilag, Tilburg, the Netherlands 3: 3 Tibotec BVBA, Mechelen, Belgium The full text article is available for purchase $54.TAX Pressing the buy now button more than once may result in multiple purchases CREDIT/DEBIT CARD INSTITUTIONAL PAYMENT ACCOUNT OR Purchase later Key: - Free Content - New Content - Subscribed Content - Free Trial Content Website 2008 Ingenta.Read more Responsiveness of the adult attention-deficit/hyperactivity disorder quality of life scale (aaqol)
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