PMID- 16164493
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20131121
IS  - 0269-4727 (Print)
IS  - 0269-4727 (Linking)
VI  - 30
IP  - 5
DP  - 2005 Oct
TI  - Safety, tolerability, and pharmacokinetics of TAS-108 in normal healthy 
      post-menopausal female subjects: a phase I study on single oral dose.
PG  - 459-70
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.
FAU - Yamaya, H
AU  - Yamaya H
AD  - Pharmacokinetics Research Laboratory, Taiho Pharmaceutical Co., Ltd, Tokushima, 
      Japan. hide-yamaya@taiho.co.jp
FAU - Yoshida, K
AU  - Yoshida K
FAU - Kuritani, J
AU  - Kuritani J
FAU - Yonezawa, J
AU  - Yonezawa J
FAU - Tsuda, M
AU  - Tsuda M
FAU - Shindo, T
AU  - Shindo T
FAU - Nagayama, S
AU  - Nagayama S
FAU - Buzdar, A U
AU  - Buzdar AU
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Hormones)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 0 (TS 108)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
EIN - J Clin Pharm Ther. 2006 Apr;31(2):204. Yonezawa, JI [corrected to Yonezawa, J]
MH  - Adult
MH  - Aged
MH  - Area Under Curve
MH  - Blood Specimen Collection
MH  - Chromatography, High Pressure Liquid
MH  - Dose-Response Relationship, Drug
MH  - Estradiol/adverse effects/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - Food-Drug Interactions
MH  - Hormones/blood
MH  - Humans
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Postmenopause/*physiology
MH  - Selective Estrogen Receptor Modulators/*adverse effects/*pharmacokinetics
EDAT- 2005/09/17 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/09/17 09:00
PHST- 2005/09/17 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/09/17 09:00 [entrez]
AID - JCP673 [pii]
AID - 10.1111/j.1365-2710.2005.00673.x [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2005 Oct;30(5):459-70. doi: 10.1111/j.1365-2710.2005.00673.x.