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Pharmacokinetics of Efavirenz When Co-administered With Rifampin in TB/HIV Co-infected Patients: Pharmacogenetic Effect of CYP2B6 Variation

From The Miriam Hospital, Providence, Rhode Island (Dr Kwara); Warren Alpert Medical School of Brown University, Providence, Rhode Island (Dr Kwara); University of Ghana Medical School, Accra, Ghana (Dr Lartey, Mr Sagoe, Mr Boamah), Korle-Bu Teaching Hospital, Accra, Ghana (Dr Xexemeku, Dr Kenu, Dr Oliver-Commey, Dr Boima, Mr Sagoe); and Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts (Dr Greenblatt and Dr Court).

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 µgxh/mL, P < .0001) or GG genotype (107 vs 23.0 µgxh/mL, P < .0001). Apparent oral clearance (CL/F) 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 CL/F 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.

Key Words: Cytochrome P450 2B6 • genetic polymorphisms • efavirenz exposure • rifampin

Address for reprints: Awewura Kwara, MD, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906; e-mail: akwara{at}lifespan.org.

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