Medicines Evaluation Board, Utrecht, the Netherlands.
Department of Epidemiology, CAPHRI, Maastricht University, the Netherlands.
Clin Pharmacol Ther. 2018 Nov;104(5):966-973. doi: 10.1002/cpt.1023. Epub 2018 Feb 13.
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.
当已确定仿制药与原研药具有生物等效性时，可以进行替代。然而，众所周知，在不同制剂之间转换时，并非所有个体患者在所有情况下的暴露相似性都能实现。我们研究的最终目的是调查当受试者暴露于生物等效制剂时是否存在药代动力学亚群。为此，我们开发了一种基于之前进行的生物利用度研究的加巴喷丁药代动力学模型，该研究比较了健康受试者中给予加巴喷丁原研药和三种加巴喷丁仿制药后加巴喷丁的暴露情况。内部和外部验证均证实，用于描述这项生物利用度研究中加巴喷丁药代动力学的最佳模型是一个两室模型，具有吸收常数、吸收时滞和肾功能调整后的清除率，其中每个模型参数都分别按给予的制剂进行估计。
