title: Pharmacokinetics and pharmacodynamics of a new long-acting androgen ester: maintenance of physiological androgen levels for 4 months after a single injection.
abstract: 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 (E2) 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 pharmacokinetic properties and may prove to be the androgen of choice for supplementation therapy in contraceptive regimens.
authors.affiliation: Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi.
authors.forename: M
authors.initials: M
authors.lastname: Rajalakshmi
authors.forename: P R
authors.initials: PR
authors.lastname: Ramakrishnan
mesh_terms: D000728:Androgens / Q000097:blood*; D000818:Animals; D013196:Dihydrotestosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006801:Humans; D007273:Injections, Intramuscular; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000728:Androgens; D006065:Gonadotropins, Pituitary; D013196:Dihydrotestosterone; C050320:testosterone 4-n-butylcyclohexylcarboxylic acid; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone