抄録
The inter- and intra-trial variability of maximum plasma concentration, a pharmacokinetics parameter of standard products, was investigated for various generic products (GEs) in biological equivalence clinical studies. A correlation between such variability and the typical physical properties of the GEs was also investigated. The product with the maximum inter-trial variability was an ethyl icosapentate GE, and that with the minimum variability was a theophylline one. The average value of the coefficient of inter-trial variation (CVc) of all the investigated GEs was 24.6±1.8% (mean ± standard error). In addition, there was significant positive correlation between CVc and LogP, a lipophilic parameter. This suggests that the absorption of medicines with high lipophilicity was greatly influenced by the intestinal condition factors of subjects, such as the elapsed time after a meal, the content of the meal and volume of water drunk with the medicine; which caused the inter-trial variability.
On the other hand, intra-trial variability was high for medicines that were substrates of metabolic enzymes and/or transporters with genetic polymorphism and it was thought that this was a major reason for the individual pharmacokinetic differences of these medicines.
