Quantitative Analysis of the ABCG2 c.421C>A Polymorphism Effect on In Vivo Transport Activity of Breast Cancer Resistance Protein (BCRP) Using an Intestinal Absorption Model. Issue 9 (30th January 2015)

• Record Type: Journal Article
• Authors: Tanaka, Yuta; Kitamura, Yoshiaki; Maeda, Kazuya; Sugiyama, Yuichi; Donovan, Maureen D.; Langguth, Peter; Polli, James E.; Tamai, Ikumi; Vig, Balvinder; Yu, Lawrence X.
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 9(2015:Sep.)
• Page Start: 3039
• Page End: 3048
• Publication Date: 2015-01-30
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24366
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>ABCG2</italic> c.421C&gt;A is one of the most frequent polymorphisms in <italic>ABCG2</italic>, which encodes the breast cancer resistance protein (BCRP). Clinical pharmacogenetic studies have shown that the plasma area under the concentration–time curve (AUC) values after oral administration of BCRP substrate drugs are significantly higher in subjects homozygous for the c.421C&gt;A polymorphism (421AA) than in wild‐type subjects (421CC). The aim of this study was to quantitatively estimate the <italic>in vivo</italic> decrease of BCRP function caused by the c.421C&gt;A polymorphism based on clinical pharmacokinetic data. Assuming that the pharmacokinetic alteration is accounted for by intestinal BCRP, the ratio of the transport activity of the mutated BCRP to that of the wild‐type was optimized by comparing calculations from an intestinal absorption model and clinical pharmacokinetic data. In conclusion, the <italic>in vivo</italic> intestinal BCRP transport activity in 421AA subjects is estimated to be approximately 23% of that in the 421CC subjects. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3039–3048, 2015</p> </abstract>