PMID- 27498100
OWN - NLM
STAT- MEDLINE
DCOM- 20170102
LR  - 20181202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 36
IP  - 12
DP  - 2016 Dec
TI  - Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic 
      Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese 
      Subjects.
PG  - 1011-1021
AB  - BACKGROUND AND OBJECTIVES: Bilastine is a novel second-generation antihistamine 
      for the symptomatic treatment of allergic rhinitis and urticaria. The objective 
      of this study was to evaluate the pharmacokinetics, pharmacodynamics, and 
      tolerability of bilastine following single and multiple oral doses in healthy 
      Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared 
      with those reported in Caucasian subjects. METHODS: In a single-blind, 
      randomized, placebo-controlled, parallel-group, single- and multiple-ascending 
      dose study, bilastine tablets were administered at single doses of 10, 20, and 
      50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II). RESULTS: 
      After single oral doses, maximum plasma concentrations (C (max)) were reached at 
      1.0-1.5 h postdose. Plasma exposure [C (max) and area under the plasma 
      concentration-time curve (AUC)] increased dose-proportionally at single doses of 
      10-50 mg. In repeated-dose administration, no remarkable differences were 
      observed between Day 1 and Day 14 for C (max) or AUC. For inhibitory effects on 
      wheal and flare response, bilastine 20 and 50 mg showed significant inhibition 
      from 1.5 h after administration as compared with placebo, and the significant 
      effect persisted for 24 h after administration. The rates of adverse events (AEs) 
      were comparable between bilastine and placebo in both Part I and Part II. In 
      addition, no dose- or administration period-dependent tendency of increase in 
      rate of AEs or worsening of severity was observed. CONCLUSION: Bilastine exhibits 
      similar single- and multiple-dose pharmacokinetic and pharmacodynamic 
      characteristics in healthy Japanese subjects compared with those observed in 
      Caucasian subjects in previous studies.
FAU - Togawa, Michinori
AU  - Togawa M
AUID- ORCID: 0000-0003-1229-3261
AD  - Project Management Department, TAIHO Pharmaceutical Co., Ltd., 1-2-4, Uchikanda, 
      Chiyoda-ku, Tokyo, 101-0047, Japan. mtogawa@taiho.co.jp.
FAU - Yamaya, Hidetoshi
AU  - Yamaya H
AD  - Tsukuba Research Center, TAIHO Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, 
      Ibaraki, 300-2611, Japan.
FAU - Rodriguez, Monica
AU  - Rodriguez M
AD  - Drug Modeling and Consulting, DynaKin, S.L. Bizkaia Technology Park, 48160, 
      Derio, Vizcaya, Spain.
FAU - Nagashima, Hirotaka
AU  - Nagashima H
AD  - Shinjuku Research Park Clinic, 1-22-17, Hyakunin-cho, Shinjuku-ku, Tokyo, 
      169-0073, Japan.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Benzimidazoles)
RN  - 0 (Histamine H1 Antagonists, Non-Sedating)
RN  - 0 (Piperidines)
RN  - PA1123N395 (bilastine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Benzimidazoles/*administration & dosage/pharmacokinetics/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Histamine H1 Antagonists, Non-Sedating/*administration & 
      dosage/pharmacokinetics/pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperidines/*administration & dosage/pharmacokinetics/pharmacology
MH  - Single-Blind Method
MH  - Young Adult
PMC - PMC5107204
COIS- Compliance with Ethical StandardsFundingThis study was funded by TAIHO 
      Pharmaceutical Co. Ltd.Conflict of interestM Togawa, and H. Yamaya are paid 
      employees of TAIHO Pharmaceutical Co. Ltd. Dr. Monica Rodriguez carried out PK/PD 
      modeling, and Dr. Nagashima was the principal investigator in this study, for 
      which they received financial compensation from TAIHO. The authors have indicated 
      that they have no other conflicts of interest with regard to the content of this 
      article.EthicsAll procedures in this study were performed in accordance with the 
      ethical standards of the institutional and/or the institutional review board, and 
      with the 1964 Helsinki declaration and its later amendments or comparable ethical 
      standards.Informed consentInformed consent was obtained from all individual 
      participants prior to their inclusion in the study.
EDAT- 2016/08/09 06:00
MHDA- 2017/01/04 06:00
PMCR- 2016/08/06
CRDT- 2016/08/08 06:00
PHST- 2016/08/09 06:00 [pubmed]
PHST- 2017/01/04 06:00 [medline]
PHST- 2016/08/08 06:00 [entrez]
PHST- 2016/08/06 00:00 [pmc-release]
AID - 10.1007/s40261-016-0447-2 [pii]
AID - 447 [pii]
AID - 10.1007/s40261-016-0447-2 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2016 Dec;36(12):1011-1021. doi: 10.1007/s40261-016-0447-2.