Danazol: prolonged suppression of gonadotropins after subcutaneous administration in the castrate male rat.

Abstract

Our purpose was to compare oral versus subcutaneous administration of danazol for its effect on elevated serum luteinizing hormone and follicle-stimulating hormone levels in castrated male rats. A single dose of danazol, either 100 or 400 mg/kg, was administered by gastric intubation or injected subcutaneously. Jugular venipuncture blood samples were taken at 0, 3, 24, and 48 hours and at 7, 10, 15, and 25 days, and serum levels of luteinizing hormone and follicle-stimulating hormone were determined by radioimmunoassay. Gonadotropin levels returned to control values 96 hours after oral administration, whereas 400 mg/kg of danazol administered subcutaneously resulted in suppression of gonadotropins for 25 days. Subcutaneous administration of danazol results in an unexpectedly prolonged suppression of serum gonadotropins compared with the same dose administered orally. A change from oral administration to a prolonged-release subcutaneous preparation of danazol may enhance the use of this drug in clinical situations and may lessen undesirable side effects.