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Clinical Trial
, 81 (6), 1078-90

Absence of Ethnic Differences in the Pharmacokinetics of Moxifloxacin, Simvastatin, and Meloxicam Among Three East Asian Populations and Caucasians

Affiliations
Clinical Trial

Absence of Ethnic Differences in the Pharmacokinetics of Moxifloxacin, Simvastatin, and Meloxicam Among Three East Asian Populations and Caucasians

Tomoko Hasunuma et al. Br J Clin Pharmacol.

Abstract

Aim: To examine whether strict control of clinical trial conditions could reduce apparent differences of pharmacokinetic (PK) parameters among ethnic groups.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Asian; difference; ethnic; extrinsic; intrinsic; pharmacokinetics.

Figures

Figure 1
Figure 1
Plasma concentration vs. time profile of (A) moxifloxacin, (B) M2 (moxifloxacin glucuronate), (C) simvastatin, (D) simvastatin acid and (E) meloxicam. Symbols and bars display the mean and SD of each group, respectively
Figure 2
Figure 2
Comparison of the Cmax and AUCinf of each drug adjusted by BW (70 kg). (A) Cmax of moxifloxacin, (B) AUCinf of moxifloxacin, (C) Cmax of M2, (D) AUCinf of M2, (E) Cmax of simvastatin, (F) AUCinf of simvastatin, (G) Cmax of simvastatin acid, (H) AUCinf of simvastatin acid, (I) Cmax of meloxicam and (J) AUCinf of meloxicam
Figure 3
Figure 3
Comparison of the AUCinf of each drug stratified by genotype (box‐and‐whisker plot without outliers (dots)). M2 (moxifloxacin glucuronate) in each UGT1A1 genotype group. Simvastatin acid in each SLCO1B1 genotype group. Meloxicam in each CYP2C9 genotype group. Boxes display the 25th to 75th percentile range, while the centre line indicates the median value, open circles indicate the mean, and closed circles indicate the outliers of each group. AUCinf is shown on the x‐axis

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