THE PHARMACOKINETICS OF CASODEX ENANTIOMERS IN SUBJECTS WITH IMPAIRED LIVER-FUNCTION

1 Casodex is a novel non-steroidal antiandrogen being developed for the treatment of prostatic cancer. The antiandrogenic activity is predominantly in the R(-) enantiomer with little, if any, activity in the S(+) enantiomer. 2 The pharmacokinetics of the enantiomers of Casodex have been investigated over 28 days following a single oral dose of Casodex (50 mg) to 10 male subjects with histologically verified liver cirrhosis or fatty liver with fibrosis. Ten age matched male subjects with normal hepatic function served as a control group. 3 For both groups plasma concentrations of (S)-Casodex were lower than those for (R)-Casodex; this difference was about 10-fold at early time points and increased to about 25-fold by 24 h after dosage. 4 The kinetics of (R)-Casodex were similar in subjects with and without liver disease (C(max): 750 vs 848 ng ml-1; t(max): 24 - 30 h; t 1/2: 7.40 vs 7.22 days; AUC: 182 vs 225 mug ml-1 h). 5 The kinetics of (S)-Casodex could not be described in the majority of subjects; in the remainder the mean terminal phase half-life for both groups was less than 1 day.