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Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis

We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 contr...

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Main Authors: Ngaimisi, Eliford (Author) , Mugusi, S. (Author) , Minzi, O. (Author) , Sasi, P. (Author) , Riedel, Klaus-Dieter (Author) , Suda, A. (Author) , Ueda, N. (Author) , Janabi, M. (Author) , Mugusi, F. (Author) , Haefeli, Walter E. (Author) , Bertilsson, L. (Author) , Burhenne, Jürgen (Author) , Aklillu, E. (Author)
Format: Article (Journal)
Language:English
Published: 03 August 2011
In: Clinical pharmacology & therapeutics
Year: 2011, Volume: 90, Issue: 3, Pages: 406-413
ISSN:1532-6535
DOI:10.1038/clpt.2011.129
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/clpt.2011.129
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1038/clpt.2011.129
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Author Notes:E Ngaimisi, S Mugusi, O Minzi, P Sasi, K-D Riedel, A Suda, N Ueda, M Janabi, F Mugusi, WE Haefeli, L Bertilsson, J Burhenne and E Aklillu
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Summary:We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction. Clinical Pharmacology & Therapeutics (2011) 90 3, 406-413. doi:10.1038/clpt.2011.129
Item Description:Gesehen am 22.09.2022
Physical Description:Online Resource
ISSN:1532-6535
DOI:10.1038/clpt.2011.129

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