Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir

In an open-label, randomized, multicenter, multiple-dose pharmacokinetic st udy, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. Th e results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUC(ss)] and 37% for peak plasma concentration at st eady state [C-max,C-ss]) and increased by indinavir (33% for AUC(ss)). Nelf inavir significantly increased amprenavir minimum drug concentration at ste ady state (by 189%) but did not affect amprenavir AUC(ss) or C-max,C-ss. Ne lfinavir and saquinavir steady-state pharmacokinetics were unchanged by coa dministration with amprenavir compared with the historical monotherapy data . Concentrations of indinavir, coadministered with amprenavir, in plasma de creased in both single-dose and steady-state evaluations. The changes in am prenavir steady-state pharmacokinetic parameters, relative to those for amp renavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-gl ycoprotein transport. No dose adjustment of either protease inhibitor in an y of the combinations studied is needed.