title: Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2 genetic variants.
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).
authors.affiliation: *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.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Tsunefusa
authors.initials: T
authors.lastname: Hayashida
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D019380:Anti-HIV Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011760:Pyrrolidinones / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000068898:Raltegravir Potassium
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D009363:Neoplasm Proteins; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium