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Effects of the slco1b1*15 allele on the pharmacokinetics of pitavastatin

Academic Article
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Overview

authors

  • Choi, C. I.
  • Lee, Y. J.
  • Lee, H. I.
  • Kim, B. H.
  • Kim, M. J.
  • Jang, Choon-Gon
  • Bae, J. W.
  • Lee, S. Y.

publication date

  • May 2012

journal

  • Xenobiotica  Journal

abstract

  • The hepatic uptake of pitavastatin is mediated by carriers, especially OATP1B1, which is encoded by the SLCO1B1 gene. Because the liver is a target organ of pitavastatin, OATP1B1 is responsible for both the pharmacological effects and clearance of pitavastatin. The effects of the SLCO1B1*15 allele on the pharmacokinetics (PK) of pitavastatin were studied. Pitavastatin 2 mg was orally administered to 38 subjects with SLCO1B1*1a/*1b (n = 20), *1b/*15 (n = 13), or *15/*15 (n = 5). After pitavastatin administration, the plasma concentrations of pitavastatin and pitavastatin lactone were assayed for up to 48 h using liquid chromatography-tandem mass spectrometry. In comparison to the SLCO1B1*1a/*1b subjects, only a C(max) was slightly higher in the SLCO1B1*1b/*15 subjects. However, the SLCO1B1*15/*15 subjects had a 1.74-fold higher AUC(inf) (285.5 ± 14.5 vs. 164.6 ± 41.3 ng·h/mL; p < 0.001), a 2.21-fold higher C(max) (106.7 ± 15.1 vs. 48.3 ± 13.4 ng/mL; p < 0.001), and a 47.3% lower apparent oral clearance (13.1 ± 3.9 vs. 6.9 ± 0.4 L/h; p < 0.001) of pitavastatin. For pitavastatin lactone, there were no significant differences in AUC(inf), C(max), t(1/2), and t(max) among the three genotypes. Unlike previous studies, the disposition of pitavastatin exposure was not altered in subjects with the SLCO1B1*1b/*15 genotype, except C(max). However, pitavastatin exposure was significantly increased in subjects with the SLCO1B1*15/*15 genotype due to reduced hepatic absorption.

subject areas

  • Administration, Oral
  • Alleles
  • Dose-Response Relationship, Drug
  • Humans
  • Organic Anion Transporters
  • Quinolines
  • Time Factors
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Identity

International Standard Serial Number (ISSN)

  • 0049-8254

Digital Object Identifier (DOI)

  • 10.3109/00498254.2011.632030

PubMed ID

  • 22077103
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Additional Document Info

start page

  • 496

end page

  • 501

volume

  • 42

issue

  • 5

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