Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity.
OBJECTIVE
Because the large increase in luteinizing hormone secretion induced by flutamide in the intact rat is not found in men, we have used castrated rats and mice supplemented with androstenedione (4-dione) instead of intact animals to measure the activity of the pure antiandrogens flutamide and Casodex.


METHODS
We first compared the effect of different schedules of administration of various doses of the two antiandrogens on prostate and seminal vesicle weights in the castrated rat and mice models.


RESULTS
For both flutamide and Casodex, no consistent difference was found between the effects of once daily and thrice daily oral dosing in the rat. It was observed, however, that flutamide, especially at the high and therapeutically more effective doses, is about three times more potent than Casodex under both schedules of dosing. When flutamide was administered subcutaneously three times a day, twice a day, once a day, or once every second day in rats and mice, no difference was observed in the degree of inhibition achieved on prostate and seminal vesicle weights.


CONCLUSIONS
The present data show that Casodex is about three times less potent than flutamide on the well-recognized parameters of androgen responsiveness in the rat, namely prostate and seminal vesicle weights. Another finding is that once daily dosing with flutamide exhibits an effectiveness comparable to thrice daily dosing; such data may have potential significance in facilitating compliance by administration of flutamide once daily instead of the current thrice daily schedule in men. Moreover, these data, if obtained in a reliable in vivo model, should be helpful in determining the choice of an appropriate dose of Casodex for the treatment of prostate cancer.
Luo
S
S
MRC Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Martel
C
C
Chen
C
C
Labrie
C
C
Candas
B
B
Singh
S M
SM
Labrie
F
F
D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000735:Androstenedione / Q000008:administration & dosage; D000813:Anilides / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005485:Flutamide / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D004343:Drug Implants; D009570:Nitriles; D014105:Tosyl Compounds; D000735:Androstenedione; D005485:Flutamide; C053541:bicalutamide