title: Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians.
abstract: To examine whether strict control of clinical trial conditions could reduce apparent differences of pharmacokinetic (PK) parameters among ethnic groups.
  
  
  
  Open-label, single dose PK studies of moxifloxacin, simvastatin and meloxicam were conducted in healthy male subjects from three East Asian populations (Japanese, Chinese and Koreans) and one Caucasian population as a control. These three drugs were selected because differences in PK parameters have been reported, even though the backgrounds of these East Asian populations are similar. Moxifloxacin (400 mg) was administered orally to 20 subjects, and plasma and urine levels of moxifloxacin and its metabolite (M2) were measured. Simvastatin (20 mg) was given to 40 subjects, and plasma levels of simvastatin and simvastatin acid were measured. Meloxicam (7.5 mg) was given to 30 subjects and its plasma concentration was determined. Intrinsic factors (polymorphism of UGT1A1 for moxifloxacin, SLCO1B1 for simvastatin, and CYP2C9 for meloxicam) were also examined.
  
  
  
  AUCinf values for moxifloxacin, simvastatin and meloxicam showed no significant differences among the East Asian groups. Cmax values of moxifloxacin and simvastatin, but not meloxicam, showed significant differences. There were no significant differences of data for M2 or simvastatin acid. Genetic analysis identified significant differences in the frequencies of relevant polymorphisms, but these differences did not affect the PK parameters observed.
  
  
  
  Although there were some differences in PK parameters among the three East Asian groups, the present study performed under strictly controlled conditions did not reproduce the major ethnic differences observed in previous studies.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.|Biomedical Research Center, Kitasato Institute Hospital, Kitasato University, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hasunuma
authors.affiliation: Department of Regulatory Science, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.|Division of Medicinal Safety Science, National Institute of Health Science, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tohkin
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Science, Tokyo, Japan.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Peking University First Hospital, Beijing, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Yimin
authors.affiliation: SNBL Clinical Pharmacology Center, Baltimore, Maryland, USA.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Science, Tokyo, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Clinical Medicine, School of Pharmacy, Kitasato University, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yamazoe
authors.affiliation: Analysis Division, Office of Safety I, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Uyama
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics; D008297:Male; D000077239:Meloxicam; D000077266:Moxifloxacin; D011110:Polymorphism, Genetic / Q000235:genetics; D019821:Simvastatin / Q000097:blood / Q000493:pharmacokinetics*; D013843:Thiazines / Q000097:blood / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000097:blood / Q000493:pharmacokinetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D065729:Cytochrome P-450 CYP2C9; D024841:Fluoroquinolones; D014453:Glucuronosyltransferase; D027381:Liver-Specific Organic Anion Transporter 1; D000077239:Meloxicam; D000077266:Moxifloxacin; D019821:Simvastatin; D013843:Thiazines; D013844:Thiazoles; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human
keywords: Asian; difference; ethnic; extrinsic; intrinsic; pharmacokinetics