Pharmacokinetics and pharmacodynamics of a new long-acting androgen ester : Maintenance of physiological androgen levels for 4 months after a single injection

The pharmacokinetics and pharmacodynamics of testosterone trans-4-n-butylcyclohexyl carboxylate (Code name: 20 Aet-1), a new long-acting androgen ester, were evaluated in castrated adult rhesus monkeys and compared with those of testosterone enanthate (TE). A single intramuscular injection of 40 mg of 20 Aet-1 returned serum testosterone (T) to within or close to the diurnal physiological range for 80–136 days. In contrast, a similar dose of TE increased serum T to supraphysiological levels and the response evoked was of short duration. The ratio of T to dihydrotestosterone (T/DHT) ratio in monkeys treated with 20 Aet-1 was comparable to that found in control animals while in TE-treated animals, it was highly elevated. Serum estradiol (E 2) elevation by 20 Aet-1 was also of smaller magnitude compared to TE. 20-Aet-1 suppressed LH levels from day 5 until day 115. The levels of LH on day 115 were 45.8% lower compared to the levels on day 13 post-castration. TE suppressed LH levels from day 1–7 post-injection. The values on day 7 were 76.6% lower compared to values on day 13 post-castration. Thus, TE-induced suppression of LH was of shorter duration, but of greater magnitude compared to the effect caused by 20 Aet-1. Similarly, FSH was suppressed for a longer duration (days 21–74) by 20 Aet-1 than by TE. The results indicate that the new testosterone ester has highly favourable pharmaco-kinetic properties and may prove to be the androgen of choice for supplementation therapy in contraceptive regimens.