期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 48, 期 9, 页码 1032-1040出版社
WILEY
DOI: 10.1177/0091270008321790
关键词
cytochrome P4502B6; genetic polymorphisms; efavirenz exposure; rifampin
资金
- NIAID NIH HHS [K23 AI071760, K23 AI071760-01, R21 AI058784-02, P30 AI042853, R21 AI058784, AI-58784, P30AI042853] Funding Source: Medline
- NIA NIH HHS [R01 AG017880, AG-17880, R01 AG017880-05] Funding Source: Medline
- NIGMS NIH HHS [R01 GM061834, R21 GM074369, R21 GM074369-01, R01 GM061834-07, GM-74369, GM-68134] Funding Source: Medline
The goal of this study was to determine the effect of CYP2B6 genetic variation on the steady-state pharmacokinetics of efavirenz (600 mg/d) in TB/HIV co-infected patients receiving concomitant rifampin, a potent CYP inducer. In the 26 patients studied, CYP2B6 c.516GG, GT and TT genotype frequencies were 0.27, 0.50, and 0.23, respectively. Mean plasma efavirenz area under the curve was significantly higher in patients with CYP2B6 c.516TT than in those with GT (107 vs 27.6 mu g.h/mL, P <.0001) or GG genotype (107 vs 23.0 mu g.h/mL, P <.0001). Apparent oral clearance (GLIF) was significantly lower in patients with CYP2B6 c.516TT than in those with GT genotype (2.1 vs 8.4 mL/min/kg, P < 0.0001) and GG genotype (2.1 vs 9.9 mL/min/kg, P <.0001). No differences in efavirenz exposure or GLIF existed between patients with CYP2B6 c.516GT and GG genotypes. Our results indicate that CYP2B6 c.516TT genotype can be used to identify efavirenz poor metabolizers in patients co-treated with rifampin.
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