Effects of CYP2B6 Genetic Polymorphisms on Efavirenz Pharmacokinetics

Summary

1. To see how the liver breaks down efavirenz by an enzyme called CYP2B6. It is suggested that when Efavirenz is taken repeatedly it may increase the amount of CYP2B6 in your liver and thus speed up your liver's ability to get rid of efavirenz from your body. This may render efavirenz and other medications ineffective. 2. To see how efavirenz interact with other drugs taken at the same time with it. 3. To see if genetic differences can change the way how the liver breaks down efavirenz and its interactions with other co-administered drugs.

Timeline

Start

2007-05

Primary completion

2010-04

Completion

2010-04

Publications

• Background Turpeinen M, Raunio H, Pelkonen O. The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metab. 2006 Oct;7(7):705-14. doi: 10.2174/138920006778520633.
• Background Hodgson E, Rose RL. The importance of cytochrome P450 2B6 in the human metabolism of environmental chemicals. Pharmacol Ther. 2007 Feb;113(2):420-8. doi: 10.1016/j.pharmthera.2006.10.002. Epub 2006 Oct 24.
• Background Ekins S, Wrighton SA. The role of CYP2B6 in human xenobiotic metabolism. Drug Metab Rev. 1999 Aug;31(3):719-54. doi: 10.1081/dmr-100101942. No abstract available.
• Background Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, Eichelbaum M, Schwab M, Zanger UM. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001 Jul;11(5):399-415. doi: 10.1097/00008571-200107000-00004.
• Background Lang T, Klein K, Richter T, Zibat A, Kerb R, Eichelbaum M, Schwab M, Zanger UM. Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther. 2004 Oct;311(1):34-43. doi: 10.1124/jpet.104.068973. Epub 2004 Jun 9.
• Background Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck WH, Eichelbaum M, Schwab M, Zanger UM. Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics. 2005 Dec;15(12):861-73. doi: 10.1097/01213011-200512000-00004.
• Collins KS, Aruldhas BW, Metzger IF, Lu JBL, Heathman MA, Quinney SK, Desta Z. A Population Pharmacokinetic Approach to Understand the Effect of Efavirenz on CYP3A Activity in Healthy Volunteers Using Midazolam as a Probe. CPT Pharmacometrics Syst Pharmacol. 2025 Dec;14(12):2095-2106. doi: 10.1002/psp4.70116. Epub 2025 Sep 24.
• Robarge JD, Metzger IF, Lu J, Thong N, Skaar TC, Desta Z, Bies RR. Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01813-16. doi: 10.1128/AAC.01813-16. Print 2017 Jan.
• Metzger IF, Quigg TC, Epstein N, Aregbe AO, Thong N, Callaghan JT, Flockhart DA, Nguyen AT, Stevens CK, Gupta SK, Desta Z. Substantial effect of efavirenz monotherapy on bilirubin levels in healthy volunteers. Curr Ther Res Clin Exp. 2014 Sep 27;76:64-9. doi: 10.1016/j.curtheres.2014.05.002. eCollection 2014 Dec.

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