Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2 genetic variants

Kiyoto Tsuchiya; Tsunefusa Hayashida; Akinobu Hamada; Shingo Kato; Shinichi Oka; Hiroyuki Gatanaga

doi:10.1097/QAI.0000000000000222

Low raltegravir concentration in cerebrospinal fluid in patients with ABCG2 genetic variants

Kiyoto Tsuchiya, Tsunefusa Hayashida, Akinobu Hamada, Shingo Kato, Shinichi Oka, Hiroyuki Gatanaga

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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).

Original language	English
Pages (from-to)	484-486
Number of pages	3
Journal	Journal of Acquired Immune Deficiency Syndromes
Volume	66
Issue number	5
DOIs	https://doi.org/10.1097/QAI.0000000000000222
Publication status	Published - 2014 Aug 15

Keywords

Adenosine triphosphate-binding cassette transporter G2
Antiretroviral therapy
Blood-cerebrospinal fluid barrier
Cerebrospinal fluid concentrations
Raltegravir

ASJC Scopus subject areas

Infectious Diseases
Pharmacology (medical)

Access to Document

10.1097/QAI.0000000000000222

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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).",

keywords = "Adenosine triphosphate-binding cassette transporter G2, Antiretroviral therapy, Blood-cerebrospinal fluid barrier, Cerebrospinal fluid concentrations, Raltegravir",

author = "Kiyoto Tsuchiya and Tsunefusa Hayashida and Akinobu Hamada and Shingo Kato and Shinichi Oka and Hiroyuki Gatanaga",

year = "2014",

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AU - Tsuchiya, Kiyoto

AU - Hayashida, Tsunefusa

AU - Hamada, Akinobu

AU - Kato, Shingo

AU - Oka, Shinichi

AU - Gatanaga, Hiroyuki

PY - 2014/8/15

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AB - 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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