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https://hdl.handle.net/2440/44525
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Type: | Journal article |
Title: | Predictive value of known and novel alleles ofCYP2B6 for efavirenz plasma concentrations in HIV-infected individuals |
Author: | Rotger, M. Tegude, H. Colombo, S. Cavassini, M. Furrer, H. Decosterd, L. Blievernicht, J. Saussele, T. Gunthard, H. Schwab, M. Eichelbaum, M. Telenti, A. Zanger, U. |
Citation: | Clinical Pharmacology and Therapeutics, 2007; 81(4):557-566 |
Publisher: | Mosby Inc |
Issue Date: | 2007 |
ISSN: | 0009-9236 1532-6535 |
Abstract: | To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy-seven (45.5%) individuals carried a known (CYP2B66,11,15, or 18) or new loss/diminished-function alleles. Resequencing defined two new loss-of-function alleles: allele 27 (marked by 593T>C [M198T]), that results in 85% decrease in enzyme activity and allele 28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 g h/ml for individuals homozygous for a loss/diminished-function allele, 58.6 g h/ml for carriers, and 43.7 g h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11–110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels. |
Keywords: | COS Cells Animals Humans HIV Infections Alkynes Cyclopropanes Oxazines Benzoxazines Aryl Hydrocarbon Hydroxylases Oxidoreductases, N-Demethylating Anti-HIV Agents Blotting, Western Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Area Under Curve Prospective Studies Predictive Value of Tests Genotype Polymorphism, Single Nucleotide Alleles Exons Plasmids Adult Female Male Cytochrome P-450 CYP2B6 Chlorocebus aethiops |
Description: | © 2008 American Society for Clinical Pharmacology and Therapeutics |
DOI: | 10.1038/sj.clpt.6100072 |
Published version: | http://dx.doi.org/10.1038/sj.clpt.6100072 |
Appears in Collections: | Aurora harvest Pharmacology publications |
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