Interchangeability of generic drugs for subpopulations: bioequivalence simulation from a non-parametric PK model of gabapentin generic drugs

Pieter J Glerum*, Walter M Yamada, Michael N Neely, David M Burger, Marc Maliepaard, Cees Neef

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


UNLABELLED: Patients are often switched between generic formulations of the same drug, but in some cases generic interchangeability is questioned. For generic drugs to be approved, bioequivalence with the innovator drug should be demonstrated; however, evidence of bioequivalence is not required in the intended patient population or relative to other approved generics.

AIM: We aim to identify pathophysiological pharmacokinetic subpopulations for whom there is a difference in comparative bioavailability, compared to a healthy population.

METHODS: We used simulated exposures from a non-parametric model of multiple generics and the originator gabapentin. Exposure was simulated for virtual populations with pharmacokinetic characteristics beyond those of the healthy subjects, with regard to rate of absorption, volume of distribution and reduced renal function. Virtual parallel design bioequivalence studies were performed using a random sample of 24 simulated subjects, with standard acceptance criteria.

RESULTS: Results indicate increased pharmacokinetic variability for patient populations with a lower rate of absorption or a reduced renal function, but no change of the average comparable bioavailability ratio. This increased variability results in a reduced likelihood of demonstrating bioequivalence. Observations were similar for comparisons between all different formulations, as well as between subjects who received the identical formulation in a repeated fashion. No relevant effect was observed for simulations with increased volume of distribution.

CONCLUSION: Our simulations indicate that the reduced likelihood of demonstrating bioequivalence for subjects with altered pharmacokinetics is not influenced by a formulation switch, nor does the average comparable bioavailability ratio change. Therefore, these results support generic interchangeability and current approval requirements for generics.

Original languageEnglish
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Publication statusE-pub ahead of print - 8 Dec 2022


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