Substitution by generics is allowed when bioequivalence to the originator has been established. However, it is known that similarity in exposure may not be achieved on every occasion for all individual patients when switching between formulations. High ratios for area under the curve (AUC) and/or maximum concentration (C_max) outside the 80.00−125.00% margin can be observed upon administration of different formulations in a single individual, even though these formulations were proven to be bioequivalent.

The ultimate aim of the authors’ research was to investigate if pharmacokinetic subpopulations exist when subjects are exposed to bioequivalent formulations. For that purpose, they 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 800 mg gabapentin formulations in healthy subjects [2].

In the current part of the investigation, model building and validation is described. Both internal and external validation confirmed that the optimal model for description of the gabapentin pharmacokinetics in this comparative bioavailability study was a 2-compartment model with absorption constant, an absorption lag time and clearance adjusted for renal function, in which each model parameter (Ka, Tlag, V, KCP, KPC and Ke) was separately estimated per administered formulation.

The authors concluded that the model as described is considered fit for further analyses and simulations. They added that such future simulations using the model will aim to identify potential subpopulations of individual patients with increased risk for altered pharmacokinetics as a result of switching between bioequivalent formulations.

Conflict of interest
Some of the authors of the research paper [1]are appointed at the Medicines Evaluation Board in The Netherlands.For full details of the authors’ conflict of interest, see the research paper [1].

Abstracted by Dr PJ Glerum, Medicines Evaluation Board, Utrecht, The Netherlands.

Editor’s comment
Readers interested to learn more about interchangeability between generics are invited to visit www.gabi-journal.net to view the following manuscripts published in GaBI Journal:

Assessment of the interchangeability between generics

Adjusted indirect comparisons between generics – bioequivalence and interchangeability

GaBI Journal is indexed in Embase, Scopus, Thomson Reuters’ ESCI, and more. 

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References
1. Glerum PJ, Yu Y, Yamada WM, Neely MN, Maliepaard M, Burger DM, Neef C. Interchangeability of generic drugs: a non-parametric pharmacokinetic model of gabapentin generic drugs. Clin Pharmacol Ther. 2018 Jan 13. doi: 10.1002/cpt.1023. [Epub ahead of print]
2. Yu Y, Teerenstra S, Vanmolkot F, Neef C, Burger D, Maliepaard M. Interchangeability of gabapentin generic formulations in the Netherlands: a comparative bioavailability study. Clin Pharmacol Ther. 2013;94(4):519-24.

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