Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 82, Issue 5, Pages 541-547Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.clpt.6100190
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To investigate the contribution of genetic polymorphisms of SLCO1B1 and ABCG2 to the pharmacokinetics of a dual substrate, pitavastatin, 2mg of pitavastatin was administered to 38 healthy volunteers and pharmacokinetic parameters were compared among the following groups: 421C/C*1b/*1b (group 1), 421C/C*1b/*15 (group 2), 421C/C*15/*15 and 421C/A*15/*15 (group 3), 421C/A*1b/*1b (group 4), 421A/A*1b/*1b (group 5), and 421C/A*1b/*15 (group 6). In SLCO1B1, pitavastatin area under plasma concentration-time curve from 0 to 24 h (AUC(0-24)) for groups 1, 2, and 3 was 81.1 +/- 18.1, 144 +/- 32, and 250 +/- 57 ng h/ml, respectively, with significant differences among all three groups. In contrast to SLCO1B1, AUC(0-24) in groups 1, 4, and 5 was 81.1 +/- 18.1, 96.7 +/- 35.4, and 78.2 +/- 8.2 ng h/ml, respectively. Although the SLCO1B1 polymorphism was found to have a significant effect on the pharmacokinetics of pitavastatin, a nonsynonymous ABCG2 variant, 421C > A, did not appear to be associated with the altered pharmacokinetics of pitavastatin.
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