A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism.
A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.
Cheng
H
H
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19422.
Shum
L
L
D000284:Administration, Oral; D003198:Computer Simulation; D007408:Intestinal Absorption / Q000502:physiology*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations