title: Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: pharmacogenetic effect of CYP2B6 variation.
abstract: 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 microg x h/mL, P< .0001) or GG genotype (107 vs 23.0 microg x 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.
authors: The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA. akwara@lifespan.org
authors: Awewura
authors: A
authors: Kwara
authors: Margaret
authors: M
authors: Lartey
authors: Kwamena W
authors: KW
authors: Sagoe
authors: Fafa
authors: F
authors: Xexemeku
authors: Ernest
authors: E
authors: Kenu
authors: Joseph
authors: J
authors: Oliver-Commey
authors: Vincent
authors: V
authors: Boima
authors: Augustine
authors: A
authors: Sagoe
authors: Isaac
authors: I
authors: Boamah
authors: David J
authors: DJ
authors: Greenblatt
authors: Michael H
authors: MH
authors: Court
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D048588:Benzoxazines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D004790:Enzyme Induction; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz; D012293:Rifampin