title: A new PK equivalence test for a bridging study.
abstract: In a bridging study, the plasma drug concentration-time curve is generally used to assess bioequivalence between the two formulations. Selected pharmacokinetic (PK) parameters including the area under the concentration-time curve, the maximum plasma concentration or peak exposure (Cmax), and drug half-life (T1/2) are compared to ensure comparable bioavailability of the two formulations. Comparability in these PK parameters, however, does not necessarily imply equivalence of the entire concentration-time profile. In this article, we propose an alternative metric of equivalence based on the maximum difference between PK profiles of the two formulations. A test procedure based on Bayesian analysis and accounting for uncertainties in model parameters is developed. Through both theoretical derivation and empirical simulation, it is shown that the new method provides better control over consumer's risk.
authors.affiliation: a Statistical Sciences, MedImmune LLC , Gaithersburg , Maryland , USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Novick
authors.affiliation: b Department of Statistics , North Carolina State University , Raleigh , North Carolina , USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Statistical Sciences, MedImmune LLC , Gaithersburg , Maryland , USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Yang
mesh_terms: D001499:Bayes Theorem; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010599:Pharmacokinetics; D013810:Therapeutic Equivalency
chemical_list: D004364:Pharmaceutical Preparations
keywords: Bayesian posterior probability; bioequivalence; concentration–time curve; pharmacokinetics