DOSE PROPORTIONALITY AND POPULATION CHARACTERISTICS OF ORAL FADROZOLEHYDROCHLORIDE, AN AROMATASE INHIBITOR, IN POSTMENOPAUSAL WOMEN

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.