医薬品添付文書中の薬物動態パラメータの研究(3):－ジェネリック医薬品の生物学的同等性試験における薬物動態パラメータの試験間および試験内変動の解析－

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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.
日本医療薬学会の論文