Drug Classification and Drug Disposition Prediction

A drug's disposition depends upon the processes of absorption from a dosing site, distribution to target and other peripheral and systemic tissues, and elimination by either metabolism or excretion of unchanged drug. These processes interact to characterize drugs by their pharmacokinetic profile as observed in a plasma concentration–time curve. The pharmacokinetic profile and alterations of this profile can impact the safety and efficacy of a drug. Pharmaceutical scientists have therefore developed methods to predict absorption, distribution, metabolism, and excretion of unchanged drug as well as understand when each of these processes may be altered and by what mechanisms. In this article, we discuss our current understanding and challenges in predicting these processes. We focus on the Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS). The BCS, developed by Amidon and coworkers in 1995, is used primarily to understand absorption and grant biowaivers to drugs using permeability and solubility parameters. The BDDCS, developed by Wu and Benet in 2005, is used to qualitatively predict drug disposition and understand whether metabolizing enzymes and/or transporters will impact drug disposition. Here, we discuss the rationale, development, classification, predictive utilities, limitations, and possibilities of these approaches.