Effect of two new androgen esters on serum levels of testosterone in castrated rhesus monkey

The pharmacokinetics of two new androgen esters were tested in castrated male rhesus monkeys. A single injection of 40 mg of 20 Aet-2 (testosterone-trans-4-n-pentyl cyclohexyl carboxylate) increased serum testosterone to three times the castrate levels and was maintained nearly at this level until day 182. When given as four separate injections of 20 mg each, 20 Aet-2 increased serum testosterone within 24 hours and the peak levels were attained on day 2 (34.6 ± 6.20 nmol/L) which was more than five times the levels obtained by 40 mg 20 Aet-2 given as a single injection. This was followed by a decrease in serum testosterone until day 98 when the levels were similar to that in animals given a single injection of 20 Aet-2. Administration of 40 mg of 3 Ad (testosterone-cis-3-(n-hexyl) cyclobutane carboxylate) given as a single injection increased serum testosterone levels to reach a peak level (47.4 ± 14.64 nmol/L) on day 5 followed by a gradual decrease to castrate levels by day 70. The profile of serum testosterone in animals injected with 80 mg of 3 Ad as four separate injections was similar to that in animals given a single dose of 40 mg of 3 Ad. The data suggest a correlation between the bioavailability of the drug and the formulation of the vehicle. The possible effect of hydrolysis rate on pharmacokinetics of the drugs is discussed.