title: Effect of tipranavir/ritonavir combination on the pharmacokinetics of tadalafil in healthy volunteers.
abstract: This study evaluated the effects of single-dose administration and steady-state concentrations of tipranavir 500 mg and ritonavir 200 mg (TPV/r) combination on the pharmacokinetics of tadalafil 10 mg (TAD) in an open-label study. Seventeen healthy male volunteers received sequential dosing of the studied product: TAD (day 1) alone in a single dose for 7 days followed by TAD (day 8) in a single dose with TPV/r (500/200 mg twice daily, days 8-18). Pharmacokinetic parameters were determined in a noncompartmental analysis. The geometric mean ratio and 90% confidence interval were used to evaluate drug interactions. The effect of a single dose of TAD on the pharmacokinetics of TPV/r resulted in a small decrease in exposure after either first-dose or steady-state TPV/r (geometric mean ratios [90% confidence interval]: area under the concentration-time curve, 0.85 [0.74-0.97]). In contrast, coadministration of TAD exposure was increased significantly (2.33 [2.02-2.69]) when administered with the first dose of TPV/r but not when TPV/r steady state was reached (1.01 [0.83-1.21]). Antiretroviral activity may not be reduced, but the dose of TAD should be reduced at the start of TPV/r therapy and then a full dose can be resumed after steady state is reached.
authors.affiliation: Pharmacology Department, Pasteur University Hospital, Nice, France. garraffo.r@chu-nice.fr
authors.forename: R
authors.initials: R
authors.lastname: Garraffo
authors.forename: T
authors.initials: T
authors.lastname: Lavrut
authors.forename: S
authors.initials: S
authors.lastname: Ferrando
authors.forename: J
authors.initials: J
authors.lastname: Durant
authors.forename: N
authors.initials: N
authors.lastname: Rouyrre
authors.forename: T R
authors.initials: TR
authors.lastname: MacGregor
authors.forename: J P
authors.initials: JP
authors.lastname: Sabo
authors.forename: P
authors.initials: P
authors.lastname: Dellamonica
mesh_terms: D000328:Adult; D001682:Biological Availability; D002243:Carbolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011753:Pyrones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000009:adverse effects / Q000494:pharmacology*; D013449:Sulfonamides; D000068581:Tadalafil; D055815:Young Adult
chemical_list: D002243:Carbolines; D017320:HIV Protease Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D000068581:Tadalafil; D019438:Ritonavir; C107201:tipranavir