Bioequivalence Study Methods with Pharmacokinetic Endpoints for Topical Ophthalmic Corticosteroid Suspensions and Effects of Subject Demographics.

PURPOSE:To establish bioequivalence for topical ophthalmic corticosteroid suspensions, some of U.S. product-specific guidances (PSGs) for generic drug products recommend evaluation of aqueous humor (AH) pharmacokinetics (PK). However, the AH PK study is complex because the relationships among AH PK, subject demographics, ocular anatomy, physiology and the compounds' physicochemical characteristics are not well understood. The objective of this research is to provide an overview of the in vivo human AH studies submitted to the U.S. Food and Drug Administration (FDA) for ophthalmic corticosteroid suspensions and to investigate the impact of subject demographics on the human AH PK.METHODS:We summarized demographic data, sampling time points, sample size per time point and PK parameters to investigate correlations in the studies submitted to the FDA.RESULTS:In the evaluation of subject-specific covariates, the area under the concentration-time curves (AUC) and maximum concentrations (Cmax) were significantly different among ethnicities and age groups. Gender was not primarily associated with differences in AH PK.CONCLUSIONS:Our results suggest that the difference in ethnicity and age of the study population play an important role in the AH PK profiles of topical ophthalmic corticosteroid suspensions. Considering the subject-specific covariate effects in designing bioequivalence studies with AH PK endpoints could reduce bias from covariate imbalance and help identify true effects of formulation differences.