SidaGhanaV1, Main, Exploration, bibRecord, 000B78

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

Identifieur interne : 000B78 ( Main/Exploration ); précédent : 000B77; suivant : 000B79

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

Auteurs : A. R. Kwara [États-Unis] ; A. R. Lartey [Ghana] ; A. R. Sagoe [Ghana] ; A. R. Xexemeku [Ghana] ; A. R. Kenu [Ghana] ; A. R. Oliver-Commey [Ghana] ; A. R. Boima [Ghana] ; A. R. Sagoe [États-Unis] ; A. R. Boamah [Ghana] ; A. R. Greenblatt [États-Unis] ; A. R. Court [États-Unis]

Source :

The Journal of Clinical Pharmacology [ 0091-2700 ] ; 2008-09.

RBID : ISTEX:556AB7CAF9CB2617DAF40C435E0767B3822141F1

English descriptors

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 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.

Url:

https://api.istex.fr/document/556AB7CAF9CB2617DAF40C435E0767B3822141F1/fulltext/pdf

DOI: 10.1177/0091270008321790

Affiliations:

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<term>Alanine aminotransferase</term>
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<term>Antiretroviral therapy</term>
<term>Aspartate aminotransferase</term>
<term>Baseline characteristics</term>
<term>Body weight</term>
<term>Bupropion hydroxylation</term>
<term>Catalytic activity</term>
<term>Clearance</term>
<term>Clin</term>
<term>Clin pharmacokinet</term>
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<term>Cmin</term>
<term>Concomitant rifampin</term>
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<term>Dose reduction</term>
<term>Drug metab disp</term>
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<term>Efavirenz dose</term>
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<term>Efavirenz plasma concentrations</term>
<term>Enzyme inducers</term>
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<term>Significant differences</term>
<term>Single nucleotide polymorphism</term>
<term>Slow metabolizer phenotype</term>
<term>Study entry</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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Pharmacokinetics of Efavirenz When Co‐administered With Rifampin in TB/HIV Co‐infected Patients: Pharmacogenetic Effect of CYP2B6 Variation

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

Source :

English descriptors

Abstract

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