期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 90, 期 3, 页码 406-413出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/clpt.2011.129
关键词
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资金
- European and Developing Countries Clinical Trial partnership [2005.32030.001]
- SIDA/SAREC [HIV 2006-031, SWE 2007-270]
- Swedish Research Council, Medicine [3902]
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.
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