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Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2 genetic variants
Kiyoto Tsuchiya1, Tsunefusa Hayashida, Akinobu Hamada
1*AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan; †Department of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, Tokyo, Japan; ‡Department of Medical Oncology and Translational Research, Kumamoto University, Kumamoto, Japan; §Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; and ‖Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Abstract:
Adenosine triphosphate-binding cassette transporter G2 (ABCG2) is expressed on the cerebrospinal fluid (CSF) side of choroid plexus epithelial cells, which form the blood-CSF barrier. Raltegravir was recently identified as a substrate of ABCG2. In the present study, we analyzed the relationship between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and raltegravir concentrations in 31 plasma and 14 CSF samples of HIV-infected patients treated with raltegravir-containing regimens. The mean CSF raltegravir concentration was significantly lower in CA (25.5 ng/mL) and AA (<10 ng/mL) genotypes at position 421 in ABCG2 gene compared with CC (103.6 ng/mL) genotype holders (P = 0.016).
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