Effect of concomitant hormone replacement therapy containing estradiol and levonorgestrel on the pharmacokinetics of selegiline.
Eur J Clin Pharmacol
; 58(4): 259-63, 2002 Jul.
Article
en En
| MEDLINE
| ID: mdl-12136372
ABSTRACT
OBJECTIVE:
The aim of this study was to investigate the effect of hormone-replacement therapy (HRT) on the pharmacokinetics of the selective monoamine oxidase B inhibitor selegiline and its primary metabolites desmethylselegiline and l-metamphetamine.METHODS:
In this randomised, double-blind, cross-over trial, 12 healthy female subjects received once daily for 10 days either HRT containing 2 mg estradiol valerate and 250 microg levonorgestrel or matched placebo. On day 10, they took a single 10-mg oral dose of selegiline. The serum concentrations of selegiline, desmethylselegiline and metamphetamine were measured for 32 h.RESULTS:
There was a 59% difference ( P=0.14) in the area under the serum concentration-time curve (AUC) of selegiline during the HRT compared with the placebo phase, but only a little or no concomitant reduction in the AUC of desmethylselegiline (-7%, P=0.071) or metamphetamine (2%, P=0.614) was observed. Maximum plasma concentration (C(max)) of selegiline was not changed, but a small, statistically significant, reduction in the C(max) of desmethylselegiline (-17%, P=0.03) was seen during the HRT phase. The C(max) of methamphetamine was slightly but not significantly reduced (-5%, P=0.06). The unchanged AUC ratios of desmethylselegiline/selegiline and metamphetamine/selegiline indicate that the primary metabolism of selegiline was not affected by HRT. All study treatments were well tolerated.CONCLUSION:
Unlike oral contraceptives, HRT is not likely to have clinically significant pharmacokinetic interaction with selegiline.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Selegilina
/
Terapia de Reemplazo de Estrógeno
/
Levonorgestrel
/
Estradiol
/
Inhibidores de la Monoaminooxidasa
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Finlandia