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Sildenafil (Viagra, UK-92,480) is a novel oral agent under development for the treatment of penile erectile dysfunction. Erection is dependent on nitric oxide and its second messenger, cyclic guanosine monophosphate (cGMP). However, the relative importance of phosphodiesterase (PDE) isozymes is not clear. We have identified both cGMP- and cyclic adenosine(More)
AIMS To determine the absolute bioavailability, dose proportionality and the effects of food on the pharmacokinetics of single oral doses of sildenafil citrate. METHODS Three open-label, randomized crossover studies were conducted in healthy male subjects. Absolute bioavailability was determined by comparing pharmacokinetic data after administration of(More)
1. Pharmacokinetics were studied in mouse, rat, rabbit, dog and man after single intravenous and/or oral doses of sildenafil or [14C]-sildenafil (Viagra). 2. In man, absorption from the gastrointestinal tract was essentially complete. With the exception of male rat, Tmax occurred at approximately 1 h or less. Bioavailability was attenuated by pre-systemic(More)
AIMS To investigate the effect of the antiretroviral protease inhibitors saquinavir (soft gelatin capsule) and ritonavir on the pharmacokinetic properties and tolerability of sildenafil and to investigate the effect of sildenafil on the steady-state pharmacokinetics of saquinavir and ritonavir. METHODS Two independent, 8 day, open, randomized,(More)
AIMS To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist. METHODS Four open-label, randomized, placebo-controlled studies were conducted in healthy subjects to assess the effect of separate and distinct combinations of CYP3A4 inhibitors on the steady-state(More)
UK-427,857 (4, 4-difluoro-N-[(1S)-3-[exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl]cyclohexanecarboxamide) is a novel CCR5 antagonist undergoing investigation for use in the treatment of human immunodeficiency virus (HIV) infection. Pharmacokinetic and metabolism studies have been performed in mouse, rat,(More)
AIMS To assess the potential of known CYP3A4 inducers, with and without CYP3A4 inhibitors, to alter the pharmacokinetic profile of maraviroc. METHODS Two separate, open, randomized, placebo-controlled studies were conducted in healthy subjects. Study 1 was a 28-day parallel-group study with three treatment groups of 12 subjects each. On days 1-7, all(More)
AIMS To assess the effect of maraviroc on the pharmacokinetics of midazolam, a sensitive probe CYP3A4 substrate; lamivudine/zidovudine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs); and ethinyloestradiol/levonorgestrel, a combination oral contraceptive. METHODS Three randomized, double-blind, placebo-controlled studies were(More)
BACKGROUND Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. (More)
AIMS To investigate the effects of age and renal and hepatic impairment on the pharmacokinetics, tolerability and safety of sildenafil (single 50-mg oral dose) and its major circulating N-desmethyl metabolite, UK-103,320. METHODS Three open-label, parallel-group studies were conducted. The first study compared sildenafil pharmacokinetics, safety and(More)