Kochak G M, Smith R A, Choi R L, John V, Tipnis V, Honc F, deSilva J K, Weidler D J
Clinical Pharmacokinetics Section, Pharmaceuticals Division, CIBA-GEIGY, New York 10502.
Pharm Res. 1989 Apr;6(4):328-31. doi: 10.1023/a:1015954609527.
The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P less than 0.05) for all pharmacokinetic variables measured, AUC, Cmax, t1/2, and tmax, its contribution to the total observed variability was relatively small for AUC, t1/2, and tmax. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, Cmax, t1/2, and tmax, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.
在一项开放标签、重复单剂量生物利用度试验中，对血管紧张素转换酶抑制剂CGS 16617的受试者内和受试者间变异性进行了评估。8名健康男性志愿者在四个不同的时间分别接受了20毫克口服剂量的CGS 16617水溶液。对一个混合效应统计模型评估方差成分，其中将受试者视为一个随机因素。虽然对于所有测量的药代动力学变量（AUC、Cmax、t1/2和tmax），受试者间变异性具有统计学意义（P小于0.05），但其对总观察变异性的贡献对于AUC、t1/2和tmax相对较小。AUC、Cmax、t1/2和tmax的受试者内变异性导致的变异比例分别为70%、19%、61%和72%。讨论了与生物利用度试验和生物学变异相关的受试者内变异性大来源成分的影响。
