The ratio of first to zeroth moments of the plasma profile of an oral drug undergoing first-pass and linear reversible metabolism.
Based on the convolution integral, equations have been derived for the ratio of the first to the zeroth moments of the plasma concentration-time curve (AUMC/AUC) parameters for a drug (p) undergoing first-pass and reversible metabolism and its reversible metabolite (m). According to these equations, the AUMC/AUC of a drug administered orally and of its reversible metabolite can be related to the mean absorption times, the ratios of the fraction of the dose entering the systemic circulation to the bioavailability, the first-time fractional conversion of each compound, and the AUMC/AUC ratios after intravenous administration of each compound. The proposed approach allows a more generalized derivation method for AUMC/AUC of a drug administered orally and undergoing first-pass and reversible metabolism. It is also applicable to any other extravascular route.
Cheng
H
H
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
D000284:Administration, Oral; D001682:Biological Availability; D007275:Injections, Intravenous; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations