生物学的同等性とバイオアベイラビリティのジャーナル

概要

On the Topic of Bioavailability/Bioequivalence-Challenges with Polymorphic Metabolism

Nuggehally R Srinivas

The topic Bioavailability/Bioequivalence (BA/BE) which is a primary driving force for the introduction of generic drugs of small molecules has been discussed for several decades now [1-5]. BA/BE studies also are important for the development of new drugs as API manufacturing process and formulation options keep changing during the entire drug development paradigm. It is needless to say that BA/ BE considerations has gone through phases of considerable debate amongst pharmaceutical scientists, academic researchers, regulators and key opinion leaders. While on one hand it could be argued that there is no one single approach that could satisfy the need/requirements for all the stake holders, on the other hand there need to be an uniform yard stick to allow consistency in BA/BE assessment. Hence, the application of average bioequivalence criteria using geometric means of peak concentration (Cmax), [a measure of rate of absorption] and geometric means of area under the plasma/serum/blood concentration curve vs. time (AUCinf) [a measure of the extent of absorption] for the parent compound between test and reference formulation has been well accepted. In order for a test formulation to be bioequivalent with the reference formulation geometric means and the 90% confidence intervals of both Cmax and AUCinf ratios of test/reference should be contained within 80 -125%.