Publication: High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections
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2013-01-01
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18800920
13474367
13474367
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2-s2.0-84880504005
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Mahidol University
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SCOPUS
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Drug Metabolism and Pharmacokinetics. Vol.28, No.5 (2013), 391-397
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Chonlaphat Sukasem, Montri Chamnanphon, Napatrupron Koomdee, Apichaya Puangpetch, Siwalee Santon, Thawinee Jantararoungtong, Santirat Prommas, Wasun Chantratita, Weerawat Manosuthi High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections. Drug Metabolism and Pharmacokinetics. Vol.28, No.5 (2013), 391-397. doi:10.2133/dmpk.DMPK-12-RG-120 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/32672
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High plasma efavirenz concentration and CYP2B6 polymorphisms in Thai HIV-1 infections
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Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography. Candidate CYP2B6 polymorphisms (c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T) were conducted by real-time PCR-based allelic discrimination. The most frequent polymorphisms among this cohort were the CYP2B6 c.785A>G and c.516G>T, which had a frequency of 0.36 and 0.32, respectively. From the cases observed, two single nucleotide polymorphisms (SNPs) (c.516G>T and c.785A>G) were significantly associated with high efavirenz plasma levels (p < 0.05). The most frequent haplotypic combinations were *1/*6, *1/*1, *1/*2 and *6/*6 at a frequency of 42.0%, 32.0%, 8.0% and 7.0%, respectively. Increased plasma concentrations of efavirenz were present in individuals with CYP2B6 *6/*6 [7.210 mg/L; interquartile range (IQR), 5.0209.260] when compared to those with CYP2B6*1/*1 (1.570mg/L; IQR, 1.2952.670), p < 0.001. In our study, the impact of SNPs which are correlated with a high level of efavirenz plasma concentrations was found. The genetic configuration of SNPs which are associated with high plasma efavirenz levels may be useful in optimizing the efavirenz dose that is used in HIV-1 infected patients. © 2013 by the Japanese Society for the Study of Xenobiotics (JSSX).