Interchangeability of Generic Drugs: A Nonparametric Pharmacokinetic Model of Gabapentin Generic Drugs

Clin Pharmacol Ther. 2018 Nov;104(5):966-973. doi: 10.1002/cpt.1023. Epub 2018 Feb 13.

Abstract

Substitution by generic drugs is allowed when bioequivalence to the originator drug has been established. However, it is known that similarity in exposure may not be achieved at every occasion for all individual patients when switching between formulations. The ultimate aim of our research is to investigate if pharmacokinetic subpopulations exist when subjects are exposed to bioequivalent formulations. For that purpose, we developed a pharmacokinetic model for gabapentin, based on data from a previously conducted bioavailability study comparing gabapentin exposure following administration of the gabapentin originator and three generic gabapentin formulations in healthy subjects. Both internal and external validation confirmed that the optimal model for description of the gabapentin pharmacokinetics in this comparative bioavailability study was a two-compartment model with absorption constant, an absorption lag time, and clearance adjusted for renal function, in which each model parameter was separately estimated per administered formulation.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Administration, Oral
  • Adult
  • Computer Simulation
  • Drug Substitution*
  • Drugs, Generic / administration & dosage
  • Drugs, Generic / pharmacokinetics*
  • Female
  • Gabapentin / administration & dosage
  • Gabapentin / pharmacokinetics*
  • Gastrointestinal Absorption
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Renal Elimination
  • Reproducibility of Results
  • Statistics, Nonparametric
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Drugs, Generic
  • Gabapentin