Dose-proportional absorption of etretinate after doses of 25, 50, 75, and 100 mg.

Twelve healthy male subjects received single oral doses of etretinate, ranging from 25 to 100 mg (1 to 4 x 25-mg capsules) in an open-label, four-way randomized crossover design. Plasma concentrations of etretinate and two active metabolites were determined by a specific high-performance liquid chromatographic (HPLC) method. Analysis of variance and orthogonal contrasts were used to assess dose proportionality. Mean (+/- %CV) maximum concentrations after 25- to 100-mg doses were 133 (50), 195 (33), 261 (53), and 446 (65) ng/ml, whereas AUC0-12 values were 581 (46), 1090 (39), 1500 (52), and 2440 (63) ng.hr/ml, respectively. The test for proportionality indicated that Cmax and AUC0-12 increased proportionally with an increase in dose (P greater than 0.05).