HIV protease inhibitors, saquinavir, indinavir and ritonavir: inhibition of CYP3A4-mediated metabolism of testosterone and benzoxazinorifamycin, KRM-1648, in human liver microsomes.
The protease inhibitors, ritonavir, indinavir and saquinavir, the most potent anti-HIV drugs developed to date, interact with many drugs by competing for CYP3A4, an enzyme central to the metabolism of a wide variety of compounds. Human liver microsomes were used to compare inhibition by these three protease inhibitors. The inhibition was the greatest with ritonavir and indinavir and less potent with saquinavir.
Inaba
T
T
Department of Pharmacology, Faculty of Medicine, University of Toronto, Canada. t.inaba@utoronto.ca
Fischer
N E
NE
Riddick
D S
DS
Stewart
D J
DJ
Hidaka
T
T
D000904:Antibiotics, Antitubercular / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019469:Indinavir / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism; D012294:Rifamycins / Q000378:metabolism; D019438:Ritonavir / Q000494:pharmacology*; D019258:Saquinavir / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D000904:Antibiotics, Antitubercular; D017320:HIV Protease Inhibitors; D012294:Rifamycins; C068980:KRM 1648; D013739:Testosterone; D019469:Indinavir; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019258:Saquinavir; D019438:Ritonavir