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Pharmacokinetics of Efavirenz When Co‐administered With Rifampin in TB/HIV Co‐infected Patients: Pharmacogenetic Effect of CYP2B6 Variation
Author(s) -
Kwara Awewura,
Lartey Margaret,
Sagoe Kwamena W.,
Xexemeku Fafa,
Kenu Ernest,
OliverCommey Joseph,
Boima Vincent,
Sagoe Augustine,
Boamah Isaac,
Greenblatt David J.,
Court Michael H.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008321790
Subject(s) - efavirenz , cyp2b6 , pharmacokinetics , genotype , pharmacogenetics , concomitant , pharmacology , rifampicin , medicine , gastroenterology , therapeutic drug monitoring , human immunodeficiency virus (hiv) , biology , antiretroviral therapy , cytochrome p450 , virology , cyp3a4 , viral load , tuberculosis , genetics , pathology , metabolism , gene
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 μg·h/mL, P < .0001) or GG genotype (107 vs 23.0 μg·h/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.