Human in vivo competitive inhibition of P450 substrates: increased plasma concentrations as a function of hepatic extraction ratio and percent inhibition

J Pharm Pharm Sci. Sep-Dec 1999;2(3):89-91.

Abstract

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.

MeSH terms

  • Binding, Competitive
  • Clarithromycin / blood*
  • Clarithromycin / pharmacokinetics
  • Clarithromycin / pharmacology*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Ketoconazole / blood*
  • Ketoconazole / pharmacokinetics
  • Ketoconazole / pharmacology*
  • Liver / drug effects
  • Liver / metabolism*
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Mixed Function Oxygenases / metabolism
  • Triazolam / blood
  • Triazolam / metabolism
  • Triazolam / pharmacology

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Triazolam
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Clarithromycin
  • Ketoconazole