The effect of food on the pharmacokinetics of the bicalutamide ('Casodex') enantiomers.
'Casodex' (bicalutamide) is an orally active, non-steroidal, pure antiandrogen; it is a racemate with antiandrogenic activity residing predominantly in the (R)-enantiomer. Healthy male volunteers (n = 15) were administered single oral doses of bicalutamide (50 mg) after food and after fasting as part of a three-treatment, three-period, randomized cross-over study, with a 9 week washout. After fasting, plasma concentrations of (R)-bicalutamide were much higher than those of (S)-bicalutamide; the mean (R)-enantiomer Cmax (734 ng mL-1) was about nine times higher than the (S)-enantiomer value (84 ng mL-1). The corresponding tmax values were 19 and 3 h for (R)- and (S)-bicalutamide, respectively. Elimination of (R)-bicalutamide from plasma was monoexponential and slow (t1/2 = 5.8 d). Elimination of (S)-bicalutamide was biphasic in some volunteers but monophasic in others (terminal t1/2 =1.2 d; n = 11). There was no significant effect of food on AUC, tmax, or t1/2 data for either enantiomer. The observed slightly higher values of Cmax for (R)-bicalutamide (14%) and (S)-bicalutamide (19%), when dosing with food, achieved statistical significance. However, differences of this magnitude are unlikely to to be of any clinical relevance. These data indicate that 'Casodex' can be taken without reference to meal times; this may be of particular relevance for its indication in a disease of the elderly.
Cockshott
I D
ID
Zeneca Pharmaceuticals, Mereside, Macclesfield, Cheshire, UK.
Oliver
S D
SD
Young
J J
JJ
Cooper
K J
KJ
DC Jones
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000813:Anilides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating; D005215:Fasting / Q000097:blood; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D051381:Rats; D013237:Stereoisomerism; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D004041:Dietary Fats; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide