Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 5). Effects of repeated doses of flutamide for 2 and 4 weeks.
Flutamide, a nonsteroidal antiandrogen, was administered orally to 8-week (for the 2 week study) and 6-week-old (for the 4 week study) male Crj:CD(SD) rats at dose levels of 0 mg/kg, 60 mg/kg and 200 mg/kg daily for 2 weeks or 4 weeks in order to determine whether a 2 week treatment period is sufficient for detection of drug effects on the male reproductive system. Flutamide treatment for 4 weeks resulted in decreased organ weights of the epididymides and prostate, decreased sperm counts and Leydig cell proliferation in the testes at 60 mg/kg and 200 mg/kg. Decreased sperm motility and histological lesions in the seminiferous tubules were observed at 200 mg/kg. Flutamide treatment for 2 weeks decreased organ weight of epididymides and prostate and caused Leydig cell proliferation in the testes at 60 mg/kg and 200 mg/kg. Decreased sperm counts and sperm motility, and histological lesions in seminiferous tubules were observed at 200 mg/kg. The results of this study showed that 2 weeks treatment with flutamide causes histological lesions of testes and disorders of sperm parameters similar to those observed with 4 weeks treatment, indicating that 2 weeks treatment is sufficient for detection of effects of flutamide on the male reproductive system.
Okahara
A
A
Santen Pharmaceutical Co., Ltd., Developmental Research Division, 3-9-19 Shimoshinjo, Higashiyodogawa-ku, Osaka 533-8651, Japan.
Nomura
A
A
Tanioka
H
H
Sakamoto
H
H
Yamashita
K
K
Ikuse
T
T
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005485:Flutamide / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects
D000726:Androgen Antagonists; D005485:Flutamide