Pharmacokinetic strategies in deciphering atypical drug absorption profiles

Drug absorption is a very complex process that manifests itself through potential interaction with a host of physicochemical and physiological variables. Some factors that may affect the absorption processes include presystemic metabolism/efflux, the "absorption window" along the gastrointestinal tract, disease states, demographics (gender, age, ethnicity), and biopharmaceutical classification of solid dosage forms. Despite the complexity of the absorption processes, the analysis of the absorption kinetic data is mostly empirical, and the assumption of first-order absorption is axiomatic. Nevertheless, we often encounter irregular drug absorption profiles (such as double-peak, absorption window-type absorption profiles, etc.) that cannot be satisfactorily described by a simple first-order absorption process. The selection of an inappropriate absorption model would result in the misspecification of the pharmacokinetic model and subsequent erroneous prediction of the dosing regimen. This article presents several pharmacokinetic strategies in analyzing typical and atypical absorption profiles. The atypical absorption profiles discussed in this article include parallel first-order absorption, mixed zero-order and first-order absorption, Weibull-type absorption, absorption window with or without Michaelis-Menton absorption, time-dependent absorption, and inverse Gaussian density absorption. In any event, intravenous drug concentration-time data are generally needed to avoid the ambiguousness in the absorption analyses.