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

Awewura Kwara; Margaret Lartey; Kwamena W Sagoe; Fafa Xexemeku; Ernest Kenu; Joseph Oliver-Commey; Vincent Boima; Augustine Sagoe; Isaac Boamah; David J Greenblatt; Michael H Court

doi:10.1177/0091270008321790

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

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

Awewura Kwara, Margaret Lartey, Kwamena W Sagoe, Fafa Xexemeku, Ernest Kenu, Joseph Oliver-Commey, Vincent Boima, Augustine Sagoe, Isaac Boamah, David J Greenblatt, …

Journal of clinical pharmacology, Vol.48(9), pp.1032-1040

09/2008

DOI: https://doi.org/10.1177/0091270008321790

Handle:

https://hdl.handle.net/2376/111730

PMCID: PMC2679896

PMID: 18728241

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Abstract

efavirenz exposure

genetic polymorphisms

rifampin

Cytochrome P450 2B6

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.

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Title: Pharmacokinetics of Efavirenz when Co-administered with Rifampin in TB/HIV Co-infected Patients: Pharmacogenetic Effect of CYP2B6 Variation
Creators: Awewura Kwara - The Miriam Hospital, Providence, Rhode Island
Margaret Lartey - University of Ghana Medical School, Accra, Ghana
Kwamena W Sagoe - University of Ghana Medical School, Accra, Ghana
Fafa Xexemeku - Korle-Bu Teaching Hospital, Accra, Ghana
Ernest Kenu - Korle-Bu Teaching Hospital, Accra, Ghana
Joseph Oliver-Commey - Korle-Bu Teaching Hospital, Accra, Ghana
Vincent Boima - Korle-Bu Teaching Hospital, Accra, Ghana
Augustine Sagoe - Korle-Bu Teaching Hospital, Accra, Ghana
Isaac Boamah - University of Ghana Medical School, Accra, Ghana
David J Greenblatt - Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts
Michael H Court - Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts
Publication Details: Journal of clinical pharmacology, Vol.48(9), pp.1032-1040
Academic Unit: Veterinary Clinical Sciences, Department of
Identifiers: 99900547722801842
Language: English
Resource Type: Journal article