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Burt HJ, Riedmaier AE, Harwood MD, et al. Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis. Drug Metab Dispos. 2016;44(10):1550-61doi: 10.1124/dmd.116.071183.
Burt, H. J., Riedmaier, A. E., Harwood, M. D., Crewe, H. K., Gill, K. L., & Neuhoff, S. (2016). Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis. Drug metabolism and disposition: the biological fate of chemicals, 44(10), 1550-61. https://doi.org/10.1124/dmd.116.071183
Burt, Howard J, et al. "Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis." Drug metabolism and disposition: the biological fate of chemicals vol. 44,10 (2016): 1550-61. doi: https://doi.org/10.1124/dmd.116.071183
Burt HJ, Riedmaier AE, Harwood MD, Crewe HK, Gill KL, Neuhoff S. Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis. Drug Metab Dispos. 2016 Oct;44(10):1550-61. doi: 10.1124/dmd.116.071183. Epub 2016 Aug 04. PMID: 27493152; PMCID: PMC5034697.
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Drug Metab Dispos. 2016 Oct;44(10):1550-61. doi: 10.1124/dmd.116.071183. Epub 2016 Aug 04.

Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.

Drug metabolism and disposition: the biological fate of chemicals

Howard J Burt, Arian Emami Riedmaier, Matthew D Harwood, H Kim Crewe, Katherine L Gill, Sibylle Neuhoff

Affiliations

  1. Simcyp Limited (a Certara Company), Sheffield, United Kingdom.
  2. Simcyp Limited (a Certara Company), Sheffield, United Kingdom [email protected].

PMID: 27493152 PMCID: PMC5034697 DOI: 10.1124/dmd.116.071183

Abstract

This study aimed to derive quantitative abundance values for key hepatic transporters suitable for in vitro-in vivo extrapolation within a physiologically based pharmacokinetic modeling framework. A meta-analysis was performed whereby data on abundance measurements, sample preparation methods, and donor demography were collated from the literature. To define values for a healthy Caucasian population, a subdatabase was created whereby exclusion criteria were applied to remove samples from non-Caucasian individuals, those with underlying disease, or those with subcellular fractions other than crude membrane. Where a clinically relevant active genotype was known, only samples from individuals with an extensive transporter phenotype were included. Authors were contacted directly when additional information was required. After removing duplicated samples, the weighted mean, geometric mean, standard deviation, coefficient of variation, and between-study homogeneity of transporter abundances were determined. From the complete database containing 24 transporters, suitable abundance data were available for 11 hepatic transporters from nine studies after exclusion criteria were applied. Organic anion transporting polypeptides OATP1B1 and OATP1B3 showed the highest population abundance in healthy adult Caucasians. For several transporters, the variability in abundance was reduced significantly once the exclusion criteria were applied. The highest variability was observed for OATP1B3 > OATP1B1 > multidrug resistance protein 2 > multidrug resistance gene 1. No relationship was found between transporter expression and donor age. To our knowledge, this study provides the first in-depth analysis of current quantitative abundance data for a wide range of hepatic transporters, with the aim of using these data for in vitro-in vivo extrapolation, and highlights the significance of investigating the background of tissue(s) used in quantitative transporter proteomic studies. Similar studies are now warranted for other ethnicities.

Copyright © 2016 The Author(s).

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