Safety and Pharmacokinetics of Single-Dose Novel Oral Androgen 11ß-Methyl-19-Nortestosterone-17ß-Dodecylcarbonate in Men.
J Clin Endocrinol Metab
; 104(3): 629-638, 2019 03 01.
Article
em En
| MEDLINE
| ID: mdl-30252057
ABSTRACT
Context 11ß-Methyl-19-nortestosterone-17ß-dodecylcarbonate (11ß-MNTDC) is an orally bioavailable prodrug of 11ß-methyl-19-nortestosterone (11ß-MNT) with androgenic and progestational activity. Objectives:
(i) Quantify 11ß-MNT binding to androgen and progesterone receptors. (ii) Evaluate safety, tolerability, and serum gonadotropin and testosterone suppression by 11ß-MNTDC in men. Design andSetting:
(i) In vitro receptor binding and transactivation studies and (ii) randomized, double-blind, placebo-controlled single-dose, dose-escalating phase I study at two academic medical centers. Participants and Intervention Twelve healthy male volunteers were randomized (five active, one placebo) to escalating single oral doses (100, 200, 400, and 800 mg) of 11ß-MNTDC or placebo given with or without food. Main OutcomeMeasures:
(i) In vitro 11ß-MNT/11ß-MNTDC human receptor binding and transactivation and (ii) safety and tolerability, pharmacokinetics, and quantification of serum gonadotropin and testosterone concentrations for 24 hours following dosing.Results:
11ß-MNT avidly binds and activates human androgen and progesterone receptors, but 11ß-MNTDC has minimal activity. Single oral doses of 11ß-MNTDC were well tolerated without serious adverse events. Administration of 11ß-MNTDC with food markedly increased average 11ß-MNTDC and 11ß-MNT serum concentrations (P < 0.001 for all doses) compared with fasting with a significant dose-related effect on average serum drug concentrations (P < 0.0001). The 200-, 400-, and 800-mg doses significantly suppressed average serum testosterone concentrations (P < 0.05).Conclusions:
A single, oral dose of 11ß-MNTDC up to 800 mg administered with food is safe and well tolerated in healthy men. The active drug 11ß-MNT has androgenic and progestational activity, rapidly suppresses serum testosterone, and is a promising candidate for an effective once-daily oral male hormonal contraceptive.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticoncepcionais Masculinos
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Nandrolona
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2019
Tipo de documento:
Article