SHORT COMMUNICATIONSHigh plasma concentrations of dolutegravir in patients with ABCG2 genetic variantsTsuchiya, Kiyotoa; Hayashida, Tsunefusaa; Hamada, Akinobuc,d; Oki, Sakurakob; Oka, Shinichia,e; Gatanaga, Hiroyukia,eAuthor Information aAIDS Clinical Center bDepartment of Pharmacy, National Center for Global Health and Medicine cDepartment of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, Tokyo dDepartment of Medical Oncology and Translational Research eCenter for AIDS Research, Kumamoto University, Kumamoto, Japan Correspondence to Hiroyuki Gatanaga, MD, PhD, AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan Tel: +81 3 3202 7181; fax: +81 3 5273 6483; e-mail: [email protected] Received June 7, 2017 Accepted August 8, 2017 Pharmacogenetics and Genomics: November 2017 - Volume 27 - Issue 11 - p 416-419 doi: 10.1097/FPC.0000000000000308 Buy Metrics Abstract The ATP-binding cassette transporters B1 (ABCB1) and G2 (ABCG2) are both expressed in the intestine and known as efflux transporters of drugs. Dolutegravir was identified recently as a substrate of both ABCB1 and ABCG2. This study aimed to determine the relations between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and plasma dolutegravir concentrations. Plasma samples were obtained from 42 HIV-1-infected patients treated with dolutegravir-containing regimens 0.5–4 h after dolutegravir dosing. Plasma dolutegravir concentrations were measured by liquid chromatography–mass spectrometry. Genomic DNA was isolated from peripheral blood mononuclear cells. Genotyping of allelic variants of ABCB1 1236 C>T (rs1128503), 2677 G>T/A (rs2032582), 3435 C>T (rs1045642), 4036 A>G (rs3842), and ABCG2 421 C>A (rs2231142) was performed using the TaqMan drug metabolism assays. None of the genotypes in ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and 4036 A>G correlated with plasma dolutegravir concentration. In contrast, the mean peak plasma concentration of dolutegravir was significantly higher in the genotypes of ABCG2 421 AA (5002 ng/ml, n=3) compared with the genotypes of ABCG2 421 CC (2569 ng/ml, n=22) and ABCG2 421 CA (2479 ng/ml, n=17) (P=0.0005). The speculated peak level of plasma dolutegravir concentration was significantly higher in ABCG2 genetic variant holders, probably, at least in part, because of low expression levels of efflux transporters in the intestines associated with these genetic variants. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.