한국인의 Diazepam 약동학에 관한 연구

• 영문명: Pharmacokinetic Study of Diazepam in Koreans
• 발행기관: 대한신경정신의학회
• 저자명: 이동영 장인진 신상구
• 간행물 정보: 『신경정신의학』제34권 제4호, 1227~1237쪽, 전체 11쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 1995.07.30

영문 초록

Objects : The benzpdiazepine derivative, diazepam continues to be among the most commonly prescribed drugs in Korea. But pharmacokinetic parameters of diazepam have been derived from the studies of which subjects were western white people and there are some limitations in translation of those parameters to Koreans. Therefore, this study was performed to establish pharmacokinetic parameters of diazepam in Koreans. Methods : A single 8mg dose of diazepam was given to 12 healthy male Korean volunteers. Plasma diazepam and its active metabolite, demethyldiazepam concentrations were determined at multiple points during the next 18days(3，8hr, 1，2，3，4，5，7，9，12，15，18day) by high performance liquid chromatography and pharmacokinetic parameters were calcualted. Results : Peak plasma concentration of diazepam were reached at about 3hr and that of demethyldiazepam were achieved at about 3days. Pharmacokinetic parameters of diazepam were * elimination half-life(ti/2), 70.1 ± 25.3(mean士 SD) hour ; total clearance, 15.1± 5.0ml/ min ; volume of distribution, 1.29± (X29L/kg(85.0± 23.5L). For demethyldiazepam, elimination half-life was 126.4±64.8 hour and clearance was 11.3± 427ml/min. In addition, the individual ti/2 values of diazepam correlated signiflcantly(r2:=: 0.81, p<0.01) with those of demethyldiazepam. Conslusion : mean elimination half-life in Korean subjects obtained from this study was longer than that of white subjects. Mean total body clearance was lower in Korean subjects than white subjects. These differences in diazepam elimination kinetics might be explained by the difference in genetic polymorphism of S-mephenytoin hydroxylase, which was known to be closely associated with the metabolism of diazepam, including the frequency of poor metabolizer. The significant correlation between diazepam and demethyldiazepam in elimination half-life suggest that both diazepam and demethyldiazepam might be metabolized, at least in part, by the same cytochrome P450 enzyme

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Diazepam Demethyldiazepam Pharmacokinetics Koreans Ethnic difference Genetic polymorphism