Pharmacokinetics of droloxifene in mice, rats, monkeys, premenopausal and postmenopausal patients.
Eur J Drug Metab Pharmacokinet
; 19(1): 47-58, 1994.
Article
en En
| MEDLINE
| ID: mdl-7957452
The pharmacokinetics of droloxifene have been studied in female mice, rats, monkeys, and premenopausal and postmenopausal patients. Droloxifene was rapidly and almost completely absorbed after oral dosing. The bioavailability was 8% in mice, 18% in rats and 11% in monkeys due to extensive first-pass metabolism. Droloxifene is widely distributed as demonstrated by its large volume of distribution and the fact that radioactivity in most tissues and organs was higher than in the blood. After oral dosing, the serum and plasma concentrations of unchanged drug declined with terminal half-lives of 1.6 h in mice, 4.3 h in rats, 10.6 h in monkeys and 25 h in patients. The systemic clearance was in the order of mice > rats > monkeys, and nearly equalled the hepatic blood flow in each species. Most of the 14C from [14C]-droloxifene administered orally and i.v. to rats and monkeys was excreted in the faeces. Droloxifene was metabolized extensively by phase I and phase II metabolism. 3-methoxy-4-hydroxy droloxifene was the major metabolite in rat faeces. The metabolites in rat and monkey faeces were not so different qualitatively. Pharmacokinetic parameters were not significantly different between premenopausal and postmenopausal patients.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Menopausia
/
Antagonistas de Estrógenos
Límite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Eur J Drug Metab Pharmacokinet
Año:
1994
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Francia