Cytochrome P450 3A inhibition by atazanavir and ritonavir, but not demography or drug formulation, influences saquinavir population pharmacokinetics in human immunodeficiency virus type 1-infected adults.
Inadequate concentrations of the human immunodeficiency virus (HIV) protease inhibitor saquinavir jeopardize individual therapy success or produce side effects despite treatment according to the current guidelines. We performed a population pharmacokinetic analysis with NONMEM and determined that the steady-state pharmacokinetics of saquinavir in 136 HIV type 1-infected adults was modulated by a decrease in saquinavir CL following coadministration of the cytochrome P450 3A inhibitors ritonavir and atazanavir. In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects.
von Hentig
Nils
N
pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
Lötsch
Jörn
J
D000328:Adult; D000367:Age Factors; D000368:Aged; D000069446:Atazanavir Sulfate; D065692:Cytochrome P-450 CYP3A Inhibitors; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019258:Saquinavir / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012737:Sex Factors; D055815:Young Adult
D065692:Cytochrome P-450 CYP3A Inhibitors; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019258:Saquinavir; D019438:Ritonavir