The Study on the Bioavailability of the Phenytoin Products

페니토인 제제의 생체이용률에 관한 연구

This study was conducted to investigate the correlation between the dissolution rates and the bioavailabilities of commercial phenytoin products, and also the correlation between their biovailabilities in rabbits and those in humans. Dissolution test was conducted in pH 9. 0 alkaline borate buffer (0.2M) using basket method with seven phenytoin products commercially available. According to the dissolution rate, the phenytoin products were divided into three groups, such as rapid, intermediate and slow group. Three phenytoin products from each group were selected for the bioavailability test in rabbits and humans. The bioavailability test was carried out in rabbits and normal volunteers using cross over design. Single doses of 20mg/kg and 300mg/man were orally administered to rabbits and normal volunteers respectively. Average $C_{max}$, $t_{max}$ and AUC of three phenytoin products were determined from the serum concentration-time curve in rabbit and human experiments. The relative bioavailability evaluation was conducted using AUC of three phenytoin products. The correlations between the dissolution rate constants and bioavailabilities (AUC) of three phenytoin products in rabbits as well as those in humans were not found. Whereas, there was significant correlation between average AUC of three phenytoin products in humans and those in rabbits (r=0.993, p<0.1). From the results of this experiment, it can be concluded that the bioavailability of phenytoin products in humans may be predicted from the results of the rabbit experiment. Also it is assumed that the prediction of the bioavailability of phenytoin products in humans may be difficult from the only results of in vitro dissolution test.