Safety, tolerability, and pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects: a phase I study on single oral dose [corrected] [published erratum appears in J CLIN PHARM THER 2006 Apr;31(2):204].
OBJECTIVES: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of TAS-108 after ascending single oral doses and to analyse preliminarily the effect of food on the pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects. METHODS: Twelve he...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 30; no. 5; pp. 459 - 471 |
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| Autores principales: | , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Oct2005
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=106383356&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 106383356 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Oct2005 vid: 30 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 106383356 106383356 2009080318 10.1111/j.1365-2710.2005.00673.x NLM16164493 106383356 ppf: 459 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Safety, tolerability, and pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects: a phase I study on single oral dose [corrected] [published erratum appears in J CLIN PHARM THER 2006 Apr;31(2):204]. aug: au: Yamaya H Yoshida K Kuritani J Yonezawa J Tsuda M Shindo T Nagayama S Buzdar AU affil: Pharmacokinetics Research Laboratory, Taiho Pharmaceutical Co., Ltd, 224-2 Hiraishi, Ebisuno, Kawauchi-cho, Tokushima 771-0194, Japan; hide-yamaya@taiho.co.jp sug: subj: Antimetabolites, Antineoplastic Therapeutic Use Breast Neoplasms Drug Therapy Estrogens Drug Effects Postmenopause Administration, Oral Adult Aged Antimetabolites, Antineoplastic Pharmacokinetics Biological Availability Chromatography, Liquid Data Analysis, Statistical Descriptive Statistics Female Japan Middle Age Mass Spectrometry Human Adult: 19-44 years Aged: 65+ years Middle Aged: 45-64 years Female ab: OBJECTIVES: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of TAS-108 after ascending single oral doses and to analyse preliminarily the effect of food on the pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects. METHODS: Twelve healthy subjects participated in an open-label, ascending single-dose, alternating group, safety, tolerance, and pharmacokinetic study of TAS-108 administered orally to two groups of the subjects, one given alternating doses of 10, 40, 120 mg (group A) and the other of 20, 80, 160 mg (group B), in the fasting state. In addition, six subjects (group A) were administered an additional dose at 120 mg TAS-108 after food consumption. Plasma and urine samples for measurement of TAS-108 were analysed by validated analytical procedures using a liquid chromatographic method with tandem mass spectrometric detection (LC/MS/MS). RESULTS: There was no dose-dependent increase in any adverse events (AEs), and there were no serious AEs or deaths. TAS-108 was readily absorbed following oral administration of the 80-, 120- and 160-mg doses. Plasma TAS-108 levels steadily declined, generally in a mono-exponential manner, with overall mean t(1/2) values ranging from 3.04 to 4.43 h in the fasting groups. Administration of TAS-108 after a high-fat meal markedly increased the bioavailability of the drug. The mean C(max) and AUC(0--t) values increased after a high-fat breakfast by 182 and 191% compared with the fasting value respectively. CONCLUSIONS: In this escalating dose study of TAS-108, the drug was well tolerated by the participants. The maximum and systemic exposure to TAS-108 tended to increase with increasing dose and its bioavailability markedly increased after high-fat food intake. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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