Kochak G M, Choi R L, Entwistle E A
Clinical Pharmacokinetics and Disposition Section, Ciba-Geigy Corporation, Ardsley, New York 10502.
Pharm Res. 1993 Dec;10(12):1760-4. doi: 10.1023/a:1018930316215.
The dose proportionality of the pharmacokinetics of fadrozole was investigated in 18 healthy postmenopausal women. Fadrozole hydrochloride was administered as 0.3-, 1.0-, and 2.0-mg oral doses continuously every 12 hr for 5 days each in a Latin square design. At steady state, the dose-normalized pharmacokinetic parameters AUC and Cmax were found to be independent of the dose. In addition, no statistically significant differences in tmax were detected. It was concluded that the pharmacokinetics of fadrozole were dose proportional in the projected therapeutic dose range. The relationship between oral clearance and the demographic factors, age, weight, and height, was assessed. Oral clearance was related to total body weight but not age or height. Prospective estimates of the population components of variance showed that intersubject variance accounted for 91.7% of the total random variance. Weight variance accounted for 36.1% of the intersubject variance.
在18名健康绝经后女性中研究了法倔唑的药代动力学剂量比例关系。采用拉丁方设计，每12小时连续口服盐酸法倔唑，剂量分别为0.3毫克、1.0毫克和2.0毫克，每种剂量持续给药5天。在稳态时，发现剂量标准化的药代动力学参数AUC和Cmax与剂量无关。此外，未检测到tmax有统计学显著差异。得出结论，在预计的治疗剂量范围内，法倔唑的药代动力学呈剂量比例关系。评估了口服清除率与人口统计学因素年龄、体重和身高之间的关系。口服清除率与总体重相关，但与年龄或身高无关。对总体方差成分的前瞻性估计表明，个体间方差占总随机方差的91.7%。体重方差占个体间方差的36.1%。
