ORAL BIOAVAILABILITY AND FIRST-PASS EFFECTS

Existing experimental strategies for the in vivo evaluation of fac-tors affecting oral bioavailability have been reviewed. Based on concepts that have evolved, an integrated set of strategies emerges that appears capable of providing estimates of the indi-vidual contributions attributable to absorption, losses in the gut lumen, and first-pass elimination in the gut wall and the liver. The only assumptions are linear pharmacokinetics and constant clear-ance between treatments. These methods are also suitable for the assessment of metabolite bioavailability after drug administration and the quantitative determination of sites of biotransformation and metabolite formation in vivo. Historically, the concept of bioavailability is closely, if not exclu-sively, associated with dosage form performance. This is because the drug entity has been defined and its absorption and disposition char-acteristics per se are fixed. Recently, the application of bioavailabilit