Effect of host genetic variation on the pharmacokinetics and clinical response of NNRTIs. (January 2008)

• Record Type: Journal Article
• Authors: Saitoh, Akihiko; Spector, Stephen A
• Is Part Of: Future HIV therapy. Volume 2:Number 1(2008)
• Page Start: 69
• Page End: 81
• Publication Date: 2008-01
• Subjects: ABCB1 -- adverse effect -- clinical response -- CYP2B6 -- efavirenz -- nevirapine -- non-nucleoside reverse transcriptase inhibitors -- pharmacokinetics -- resistant virus; HIV (Viruses) -- Treatment -- Periodicals; HIV (Viruses) -- Research -- Periodicals; 616.979206
• DOI: 10.2217/17469600.2.1.69
• Languages: English
• ISSNs: 1746-9600

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been widely used for treating HIV type 1 (HIV-1)-infected patients as a component of HAART and for the prevention of mother-to-child transmission (MTCT). Cytochrome P450 (CYP)2B6 is an important hepatic isoenzyme responsible for the metabolism of NNRTIs, such as efavirenz and nevirapine. Recent pharmacogenetic studies have shown that CYP2B6 genetic variants alter hepatic CYP2B6 protein expression and function, and the pharmacokinetics of several CYP2B6 substrates. In particular, the CYP2B6 -G516T polymorphism in exon 4 affects the pharmacokinetics of efavirenz. Other studies have shown associations of the CYP2B6 -G516T genotype with nevirapine pharmacokinetics and CNS adverse effects related to efavirenz use. In total, CYP2B6 genetic variants are important determinants of efavirenz and nevirapine pharmacokinetics. Further studies are needed to identify the associations of CYP2B6 genetic variants with the development of NNRTI-resistant viruses.