PHARMACOKINETICS AND PHARMACODYNAMICS OF 7-ALPHA-METHYL-19-NORTESTOSTERONE AFTER INTRAMUSCULAR ADMINISTRATION IN HEALTHY-MEN

7 alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androge n that is resistant to 5 alpha-reductases and therefore less prone to over-stimulate the prostate, It is a good candidate for implant admini stration in long-term androgen replacement therapy for hypogonadal men or as part of a male contraceptive system, To investigate the pharmac okinetics of MENT after i.m. administration, single i.m. injections of 2, 4 or 8 mg of micronized MENT were given in aqueous suspension to 1 8 healthy men in two clinics, Blood was sampled frequently for 8 h and 1, 2, 3, 4 and 9 days after the injections, Serum MENT concentrations were determined by radioimmunoassay. Peak MENT concentrations mere do se-dependent and were reached about 1-2 h after the injections, Doubli ng the dose of MENT resulted in an increase of 60% in peak serum MENT concentrations, The mean +/- SE clearance rate mas 1790 +/- 140 l/day. The antigonadotrophic activity of MENT was investigated by giving sh consecutive daily i.m. injections of 1, 2 or 4 mg of MENT to 24 health y men in two clinics. Blood was sampled before each injection and up t o 24 days after the last injection, Serum testosterone and gonadotroph in concentrations (determined by radioimmunoassay and fluoroimmunoassa y respectively) decreased in a dose-dependent and statistically signif icant manner, The highest dose caused a 74% fall in testosterone, a 70 % fall in luteinizing hormone, and a 57% fall in follicle stimulating hormone concentrations, MENT injections did not cause any side-effects , The results show that MENT is a potent antigonadotrophic agent in me n.