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

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

Department of Medical Microbiology

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1032-1040
Number of pages	9
Journal	Journal of Clinical Pharmacology
Volume	48
Issue number	9
DOIs	https://doi.org/10.1177/0091270008321790
Publication status	Published - Sep 2008

Keywords

Cytochrome P450 2B6
Efavirenz exposure
Genetic polymorphisms
Rifampin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1177/0091270008321790

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Kwara, A., Lartey, M., Sagoe, K. W., Xexemeku, F., Kenu, E., Oliver-Commey, J., Boima, V., Sagoe, A., Boamah, I., Greenblatt, D. J., & Court, M. H. (2008). Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: Pharmacogenetic effect of CYP2B6 variation. Journal of Clinical Pharmacology, 48(9), 1032-1040. https://doi.org/10.1177/0091270008321790

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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 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.",

keywords = "Cytochrome P450 2B6, Efavirenz exposure, Genetic polymorphisms, Rifampin",

author = "Awewura Kwara and Margaret Lartey and Sagoe, {Kwamena W.} and Fafa Xexemeku and Ernest Kenu and Joseph Oliver-Commey and Vincent Boima and Augustine Sagoe and Isaac Boamah and Greenblatt, {David J.} and Court, {Michael H.}",

year = "2008",

month = sep,

doi = "10.1177/0091270008321790",

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volume = "48",

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Kwara, A, Lartey, M, Sagoe, KW, Xexemeku, F, Kenu, E, Oliver-Commey, J, Boima, V, Sagoe, A, Boamah, I, Greenblatt, DJ & Court, MH 2008, 'Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: Pharmacogenetic effect of CYP2B6 variation', Journal of Clinical Pharmacology, vol. 48, no. 9, pp. 1032-1040. https://doi.org/10.1177/0091270008321790

TY - JOUR

T1 - Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients

T2 - Pharmacogenetic effect of CYP2B6 variation

AU - Kwara, Awewura

AU - Lartey, Margaret

AU - Sagoe, Kwamena W.

AU - Xexemeku, Fafa

AU - Kenu, Ernest

AU - Oliver-Commey, Joseph

AU - Boima, Vincent

AU - Sagoe, Augustine

AU - Boamah, Isaac

AU - Greenblatt, David J.

AU - Court, Michael H.

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - Cytochrome P450 2B6

KW - Efavirenz exposure

KW - Genetic polymorphisms

KW - Rifampin

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U2 - 10.1177/0091270008321790

DO - 10.1177/0091270008321790

M3 - Article

C2 - 18728241

AN - SCOPUS:49649114600

SN - 0091-2700

VL - 48

SP - 1032

EP - 1040

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

IS - 9

ER -

Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: Pharmacogenetic effect of CYP2B6 variation

Abstract

Keywords

UN SDGs

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