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Báo cáo y học: " Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults. | Uttayamakul et al. AIDS Research and Therapy 2010 7 8 http www.aidsrestherapy.eom content 7 1 8 AIDS RESEARCH AND THERAPY RESEARCH Open Access Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV TB co-infected Thai adults 1.2 2 2 3 Sumonmal Uttayamakul 1 Sirirat Likanonsakul Weerawat Manosuthi Nuanjun Wichukchinda Th roorsỉt 1 2 N mta hof i1 Fmi p M nl sn sim 4 T-s-f-ri ir Cmir i H 4 Qricin kTi icmifh1 inaieeiai I aiamuaiieu 1 Lilli L Nakayama 1 laisuo Shioda 1 Siisin iMiusmiui Abstract Background Cytochrome P450 2B6 CYP2B6 metabolizes efavirenz and nevirapine the major core antiretroviral drugs for HIV in Thailand. Rifampicin a critical component of tuberculosis TB therapy is a potent inducer of CYP enzyme activity. Polymorphisms of CYP2B6 and CYP3A4 are associated with altered activity of hepatic enzyme in the liver and pharmacokinetics resulting in treatment efficacy. This study aimed to investigate whether CYP2B6 or CYP3A4 polymorphisms had effects on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV TB co-infected Thai adults. Results We studied 124 rifampicin recipients with concurrent HIV-1 TB coinfection receiving efavirenz 600 mg day n 65 or nevirapine 400 mg day n 59 based antiretroviral therapy ART . The frequencies of GG GT and TT genotypes of CYP2B6-G516T were 38.46 47.69 and 13.85 in efavirenz group and 44.07 52.54 and 3.39 in nevirapine group respectively. The mean 12-hour post-dose plasma efavirenz concentration in patients with TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation 10.97 2.32 13.62 4.21 and 8.48 1.30 mg L respectively were significantly higher than those with GT 3.43 0.29 3.35 0.27 and 3.21 0.22 mg L respectively p 0.0001 or GG genotypes 2.88 0.33 2.45 0.26 and 2.08 0.16 mg L respectively p 0.0001 . Likewise the mean 12-hour post-dose plasma nevirapine concentration in patients carrying TT .