Gm. Kochak et al., DOSE PROPORTIONALITY AND POPULATION CHARACTERISTICS OF ORAL FADROZOLEHYDROCHLORIDE, AN AROMATASE INHIBITOR, IN POSTMENOPAUSAL WOMEN, Pharmaceutical research, 10(12), 1993, pp. 1760-1764
The dose proportionality of the pharmacokinetics of fadrozole was inve
stigated in 18 healthy postmenopausal women. Fadrozole hydrochloride w
as administered as 0.3-, 1.0-, and 2.0-mg oral doses continuously ever
y 12 hr for 5 days each in a Latin square design. At steady state, the
dose-normalized pharmacokinetic parameters AUC and C(max) were found
to be independent of the dose. In addition, no statistically significa
nt differences in t(max) were detected. It was concluded that the phar
macokinetics of fadrozole were dose proportional in the projected ther
apeutic dose range. The relationship between oral clearance and the de
mographic factors, age, weight, and height, was assessed. Oral clearan
ce was related to total body weight but not age or height. Prospective
estimates of the population components of variance showed that inters
ubject variance accounted for 91.7% of the total random variance. Weig
ht variance accounted for 36. 1% of the intersubject variance.