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THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF THE BICALUTAMIDE (‘CASODEX’) ENANTIOMERS
Author(s) -
COCKSHOTT I. D.,
OLIVER S. D.,
YOUNG J. J.,
COOPER K. J.,
JONES D. C.
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199708)18:6<499::aid-bdd37>3.0.co;2-j
Subject(s) - bicalutamide , cmax , antiandrogen , pharmacokinetics , enantiomer , pharmacology , chemistry , endocrinology , medicine , androgen , stereochemistry , prostate cancer , hormone , cancer , androgen receptor
‘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 C max (734 ng mL −1 ) was about nine times higher than the (S)‐enantiomer value (84 ng mL −1 ). The corresponding t max values were 19 and 3 h for (R)‐ and (S)‐bicalutamide respectively. Elimination of (R)‐bicalutamide from plasma was monoexponential and slow ( t 1/2 =5·8 d). Elimination of (S)‐bicalutamide was biphasic in some volunteers but monophasic in others (terminal t 1/2 =1·2 d; n =11). There was no significant effect of food on AUC, t max , or t 1/2 data for either enantiomer. The observed slightly higher values of C max for (R)‐bicalutamide (14%) and (S)‐bicalutamide (19%), when dosing with food, achieved statistical significance. However, differences of this magnitude are unlikely 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. © 1997 John Wiley & Sons, Ltd.