A general model of metabolite kinetics following intravenous and oral administration of the parent drug.
A model of metabolite pharmacokinetics is developed in terms of residence time distributions and derived non-compartmental measures. It provides quantitative insight into factors determining the concentration-time curve of metabolite following intravenous and oral administration of the precursor drug. The AUCs and higher curve moments (mean residence times and relative dispersions) are calculated/predicted and their dependence on mean absorption time, fraction of first-pass metabolism and intrinsic disposition residence times of the parent drug and metabolite, respectively, is discussed. An AUC-based method for the determination of the first-pass effect is proposed which is not influenced by drug absorption. The approach is valid for linear pharmacokinetic systems exhibiting hepatic and renal elimination of the precursor drug; it is not restricted to specific compartmental models. Limitations of previous concepts of metabolite kinetics are defined. Criteria are presented for the appearance of concave metabolite curves in a semi-logarithmic scale.
Weiss
M
M
Department of Pharmacology and Toxicology, Martin Luther University, Halle, German Democratic Republic.
D000284:Administration, Oral; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations