Safety, tolerability and pharmacokinetics of TAS-108, a novel anti-oestrogen, in healthy post-menopausal Japanese women: a phase I single oral dose study.
Basic Clin Pharmacol Toxicol
; 104(5): 352-9, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19175362
ABSTRACT
TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the treatment of breast cancer. The present study was conducted to investigate the safety, tolerability and pharmacokinetics of TAS-108 following the administration at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and the effect of food on the pharmacokinetics of the drug. All adverse events were mild and involved transient symptoms that resolved without therapeutic intervention. TAS-108 was readily absorbed and plasma levels of TAS-108 steadily declined, apparently in a multi-exponential manner. C(max) and AUC(0-12) were proportionally increased with increasing dose of TAS-108. The C(max) and AUC(0-t) of TAS-108 and its metabolite, deEt-TAS-108, were significantly increased to approximately 150% when TAS-108 was administered after a meal. Food did not affect the elimination half-life of TAS-108 or its metabolites. In this escalating dose-study of TAS-108, the drug was well tolerated by healthy post-menopausal Japanese women. The pharmacokinetics of TAS-108 indicated dose proportionality, and its bioavailability was significantly increased by food intake.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pós-Menopausa
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Estradiol
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Antagonistas de Estrogênios
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Estrogênios
Limite:
Female
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Humans
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Middle aged
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article