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Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism.
Clin Pharmacol Ther. 2013 Jul; 94(1):37-51.CP

Abstract

Because the plasma exposure levels of rosuvastatin in Asians are generally twice those in Caucasians, the starting dose for Asians in the United States is set to half of that for non-Asians. However, the precise role of ethnicity in the clearance of rosuvastatin has not yet been clarified. This review focuses on ethnic variability in the clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (statins) and angiotensin II receptor antagonists. The mechanisms of such variability are discussed quantitatively, with building a hypothetical model for pravastatin, and validated against other statins. Our analyses suggest that the ethnic variability in the plasma exposure of statins cannot be explained only by the difference in the allele frequencies of organic anion-transporting polypeptide (OATP)1B1 and breast cancer resistance protein (BCRP), and the intrinsic ethnic variability in the activity of OATP1B1 (the ratio of Japanese/Caucasians is 0.584) must be considered. Further work and validation with additional data will clarify the applicability of this model to other OATP1B1 substrates.

Authors+Show Affiliations

Clinical Pharmacology, Department of Drug Development, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23443754

Citation

Tomita, Y, et al. "Ethnic Variability in the Plasma Exposures of OATP1B1 Substrates Such as HMG-CoA Reductase Inhibitors: a Kinetic Consideration of Its Mechanism." Clinical Pharmacology and Therapeutics, vol. 94, no. 1, 2013, pp. 37-51.
Tomita Y, Maeda K, Sugiyama Y. Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism. Clin Pharmacol Ther. 2013;94(1):37-51.
Tomita, Y., Maeda, K., & Sugiyama, Y. (2013). Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism. Clinical Pharmacology and Therapeutics, 94(1), 37-51. https://doi.org/10.1038/clpt.2012.221
Tomita Y, Maeda K, Sugiyama Y. Ethnic Variability in the Plasma Exposures of OATP1B1 Substrates Such as HMG-CoA Reductase Inhibitors: a Kinetic Consideration of Its Mechanism. Clin Pharmacol Ther. 2013;94(1):37-51. PubMed PMID: 23443754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism. AU - Tomita,Y, AU - Maeda,K, AU - Sugiyama,Y, Y1 - 2012/11/07/ PY - 2013/2/28/entrez PY - 2013/2/28/pubmed PY - 2013/8/30/medline SP - 37 EP - 51 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 94 IS - 1 N2 - Because the plasma exposure levels of rosuvastatin in Asians are generally twice those in Caucasians, the starting dose for Asians in the United States is set to half of that for non-Asians. However, the precise role of ethnicity in the clearance of rosuvastatin has not yet been clarified. This review focuses on ethnic variability in the clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (statins) and angiotensin II receptor antagonists. The mechanisms of such variability are discussed quantitatively, with building a hypothetical model for pravastatin, and validated against other statins. Our analyses suggest that the ethnic variability in the plasma exposure of statins cannot be explained only by the difference in the allele frequencies of organic anion-transporting polypeptide (OATP)1B1 and breast cancer resistance protein (BCRP), and the intrinsic ethnic variability in the activity of OATP1B1 (the ratio of Japanese/Caucasians is 0.584) must be considered. Further work and validation with additional data will clarify the applicability of this model to other OATP1B1 substrates. SN - 1532-6535 UR - https://www.unboundmedicine.com/medline/citation/23443754/Ethnic_variability_in_the_plasma_exposures_of_OATP1B1_substrates_such_as_HMG_CoA_reductase_inhibitors:_a_kinetic_consideration_of_its_mechanism_ L2 - https://doi.org/10.1038/clpt.2012.221 DB - PRIME DP - Unbound Medicine ER -