Human in vivo competitive inhibition of P450 substrates: increased plasma concentrations as a function of hepatic extraction ratio and percent inhibition.
The purpose of this note is to posit and discuss the concept of "competitive inhibition potential" (CIP), which is an in vivo index of the ability of a competitive inhibitor to elevate plasma concentrations of drug substrates, when the competitive inhibitor is administered at its usual and customary dose.
Boxenbaum
H
H
Arishel Inc., North Potomac, Maryland, USA. shelbyb@ix.netcom.com
D001667:Binding, Competitive; D017291:Clarithromycin / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007654:Ketoconazole / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014229:Triazolam / Q000097:blood / Q000378:metabolism / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D014229:Triazolam; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D017291:Clarithromycin; D007654:Ketoconazole