title: Application of mean residence-time concepts to pharmacokinetic systems with noninstantaneous input and nonlinear elimination.
abstract: Equations describing the mean residence time (MRT) of drugs in the body are derived for drugs that are administered by first- and zero-order rates into systems with Michaelis-Menten elimination. With computer simulations, the validity of these equations, the differences between them, and the conventional approach using the AUMC/AUC or the summation of mean times are demonstrated by examining calculations of the percentage of the administered dose eliminated at the MRT and AUMC/AUC. The effects of the absorption rate on the AUC and on the approximate and true MRT values in a nonlinear pharmacokinetic system are also illustrated with computer simulations. It was previously found that the true MRTiv = Vss.AUCiv/dose for an iv bolus. The total MRT (sum of input and disposition) of a drug after noninstantaneous administration was found to be a function of the MRTiv, two values of AUC (iv and non-iv), and exactly how the drug is administered expressed as the mean absorption time (MAT). In addition, a theoretical basis is proposed for calculation of the bioavailability of drugs in both linear and nonlinear pharmacokinetic systems.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
authors.forename: H Y
authors.initials: HY
authors.lastname: Cheng
authors.forename: W J
authors.initials: WJ
authors.lastname: Jusko
mesh_terms: D008433:Mathematics; D008956:Models, Chemical; D010599:Pharmacokinetics