Glaxo's Experience of Different Absorption Rate Metrics of Immediate Release and Extended Release Dosage Forms

Abstract

As indirect measures (metrics) of rate of drug absorption, Cmax is confounded by extent of drug absorption and tmax is a discrete variable, dependent on blood sampling frequency; therefore, there is a need for improved metrics of rate. Building upon the work of Endrenyi et al. (1) and Chen (2), different metrics have been compared using simulated single dose bioequivalence studies of immediate release (IR) dosage forms. Those investigated included: Cmax/AUC∞, partial AUC from zero to tmax of the reference formulation (AUCr), partial AUC from zero to tmax of the test or reference formulation, whichever occurs earliest (AUCe), and the normalized partial AUCs (AUCr/AUC∞, and AUCc/AUC∞, which like Cmax/AUC∞, are not confounded by extent of absorption) (3,4). Importantly, the performance of these metrics was further assessed using the results of several actual pharmacokinetic studies involving IR dosage forms of Glaxo drugs.For extended release (ER) dosage forms, bioequivalence assessments are carried out at s...