Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by CHESTER, A. E.
Right arrow Articles by DEPASS, L. R.
Right arrow Search for Related Content
PubMed
Right arrow Articles by CHESTER, A. E.
Right arrow Articles by DEPASS, L. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1991 Oxford University Press

research-article

Acute and Subchronic Toxicity Studies with Detirelix, a Luteinizing Hormone-Releasing Hormone Antagonist, in the Rat and Monkey

ANNE E. CHESTER1, DAVID G. FAIRCHILD and LINVAL R. DEPASS

Institute of Toxicologic Sciences, Syntex Research/R2-ITS 3401 Hillview Avenue, Palo Alto, California 94303

Received November 26, 1990; accepted April 9, 1991

Acute and Subchronic Toxicity Studies with Detirelix, a Luteinizing Hormone-Releasing Hormone Antagonist, in the Rat and Monkey. CHESTER, A. E., FAIRCHILD, D. G., AND DEPASS, L. R. (1991). Fundam. Appl. Toxicol. 17, 505–518. Acute (single dose), 2-week, and 3-month toxicology studies were conducted with detirelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, in rats and cynomolgus monkeys. Acute studies were conducted by intravenous and subcutaneous injection. Subchronic studies were conducted by daily subcutaneous injection. Clinical signs after a single intravenous dose included lethargy, edema, cyanosis, pallor, and red ears in rats at ≥ 0.3 mg/kg and lethargy and facial flushing in monkeys at ≥0.5 mg/kg, In subchronic studies, detirelix at 0.4 mg/kg/day (rats) and at ≥0.2 mg/kg/day (monkeys) produced atrophy of the reproductive organs, inhibition of ovulation and spermatogenesis, decreased body weight gain in male rats and monkeys, and increased body weight gain in female rats. In the rat, morbidity and/or mortality occurred throughout the treatment phase at a subcutaneous dose of 2.0 mg/kg/day. In both species, the time to recovery of normal reproductive organ morphology and function was directly related to dose. Exogenous testosterone decreased the severity of reproductive and body weight effects in male rats. In conclusion, the acute effects of detirelix were consistent with peripheral vasodilation. Subchronic effects were associated with inhibition of pituitary gonadotropic and gonadal hormone secretion.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.