Evaluating drug absorption after oral administration. Some problems and some solutions

Abstract

Quantitative assessment of drug absorption remains a difficult task, because the multiple-compartment disposition of a drug may not be obvious after oral administration (the problem of the vanishing exponential) and the macroconstants are indistinguishable. For these reasons, proper analysis of the drug absorption based on the apparent behavior of oral data without intravenous reference curve rarely provides absorption information useful for in vivo - in vitro correlations. When intravenous reference curve is available, compartment model used for analysis of the oral data should be corresponding to the iv data such as the Loo - Riegelman method. The model independent statistical moments method is one of the preferable alternatives because of its ease of computation and its potentially smaller error, if absorption can be assumed to be first-order.