Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 319, Issue 4, Pages 1322-1326Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.05.116
Keywords
cytochrome P450; genetic polymorphism; HIV-1; efavirenz; plasma concentration
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Efavirenz (EFV) is metabolized by cytochrome P450 2136 (CYP2B6) in the liver. We analyzed the genotypes of CYP2B6 and their contribution to plasma EFV concentrations in 35 EFV-treated patients in International Medical Center of Japan. The mean plasma EFV concentration of patients with CYP2R6 *6/*6 (Q172H and K262R) (25.4 +/- 7.5 muM, +/-SD, n = 2) was significantly higher than that of patients with genotypes *6 heterozygote (9.9 +/- 3.3 muM, n = 10) or without alleles *6 (8.0 +/- 2.6 muM, n = 23) (p < 0.0001). To confirm our result, we further analyzed nine patients (three with high EFV concentrations and arbitrarily selected six with normal EFV concentrations) treated in Osaka National Hospital, and it resulted that the only three patients with the high concentrations were the *6/*6 holder. EFV dose could be decreased in those patients harboring the genotype to reduce toxicity with compromising potency, representing the first step of the Tailor-Made therapy of HIV-1 infection. (C) 2004 Elsevier Inc. All rights reserved.
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