Mifentidine: evaluation of antiandrogen effects and kidney function studies

Among a number of investigations aimed at evaluating the safety profile of a new antihistamine (H2), N1-[(4-imidazolyl)-phenyl]-N2-isopropyl-formamidine (mifentidine), its effects on male accessory sexual organs and on kidney function were studied in greater detail because of the known propensity of H2-antagonists to cause antiandrogenic activity and to alter renal function. Mifentidine (190 and 380 mg/kg p.o.) was compared to cimetidine (475 and 950 mg/kg p.o.) for its ability to affect growth of seminal vesicles and prostate of immature castrated rats treated either with testosterone (TP) or 5-alpha-dihydrotestosterone (DHT). Lower doses of mifentidine were investigated because, in terms of H2-antagonistic activity, it was shown to be several times (15 to 30) as potent as cimetidine. Cimetidine at the highest dose (950 mg/kg) reduced prostate growth sustained by TP, and the DHT-promoted growth of seminal vesicles and prostate. Mifentidine had no effect on hormone promoted growth of male accessory sexual organs. Renal function studies after repeated (7 days) administration of mifentidine (150 and 600 mg/kg p.o.) and cimetidine (1500 mg/kg p.o.) revealed a significant increase of the excreted fraction of filtered sodium (FeNa) and potassium (FeK) only after cimetidine, indicating altered tubular reabsorption. Creatinine and urea clearances were unchanged by either drug treatment. Thus mifentidine appears to be devoid of antiandrogenic activity and renal effects.