Pharmacokinetics of Efavirenz When Co-administered With Rifampin in TB/HIV Co-infected Patients: Pharmacogenetic Effect ofCYP2B6Variation
| Autor: | Fafa Xexemeku, Ernest Kenu, Awewura Kwara, Joseph Oliver-Commey, Vincent Boima, Isaac Boamah, Augustine Sagoe, Michael H. Court, David J. Greenblatt, Margaret Lartey, Kwamena W. Sagoe |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Cyclopropanes Male Efavirenz CYP2B6 Anti-HIV Agents HIV Infections Pharmacology Biology Article chemistry.chemical_compound Gene Frequency Pharmacokinetics Genotype Humans Tuberculosis Pharmacology (medical) Prospective Studies Antibiotics Antitubercular Genetic Variation Oxidoreductases N-Demethylating Middle Aged Benzoxazines Genotype frequency Cytochrome P-450 CYP2B6 Phenotype Haplotypes chemistry Alkynes Enzyme Induction Concomitant Reverse Transcriptase Inhibitors Female Aryl Hydrocarbon Hydroxylases Rifampin Pharmacogenetics |
| Zdroj: | The Journal of Clinical Pharmacology. 48:1032-1040 |
| ISSN: | 0091-2700 |
| Popis: | The goal of this study was to determine the effect of CYP2B6 genetic variation on the steady-state pharmacokinetics of efavirenz (600 mg/day) 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 < 0.0001), or GG genotype (107 vs. 23.0 μg.h/mL, P < 0.0001). 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 < 0.0001). 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. |
| Databáze: | OpenAIRE |
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