A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.

British Journal of Clinical Pharmacology
Jackson K MukonzoEleni Aklillu

Abstract

Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM. Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. Apparent oral clearance (95% confidence interval) was 4 l h l(-1) (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The a...Continue Reading

References

Feb 7, 1998·The Journal of Clinical Investigation·R B KimG R Wilkinson
Apr 9, 1999·Computer Methods and Programs in Biomedicine·E N Jonsson, M O Karlsson
Nov 15, 2001·Journal of Acquired Immune Deficiency Syndromes : JAIDS·M NúñezV Soriano
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Marc PfisterUNKNOWN Adult AIDS Clinical Trial Group Study 398
Jan 25, 2003·Clinical Pharmacology and Therapeutics·Chantal CsajkaThierry Buclin
Apr 18, 2003·International Journal of Clinical Pharmacology and Therapeutics·J S BarrettH J Pieniaszek
Feb 26, 2004·Antimicrobial Agents and Chemotherapy·Richard C BrundageCourtney V Fletcher
May 19, 2005·Computer Methods and Programs in Biomedicine·Justin J Wilkins
Jun 15, 2007·Pharmacogenomics·Zeruesenay DestaUlrich M Zanger
Aug 21, 2007·Gender Medicine·Ighovwerha OfotokunJane E Hitti

❮ Previous
Next ❯

Citations

Jun 2, 2011·European Journal of Clinical Pharmacology·Eleni AklilluJohanna Weiss
Oct 24, 2012·The Pharmacogenomics Journal·A HabtewoldE Aklillu
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Almudena SánchezUNKNOWN Tormes Group
Dec 12, 2012·Pharmacogenomics and Personalized Medicine·Rebecca Pavlos, Elizabeth J Phillips
Jul 12, 2011·Clinical Pharmacokinetics·Jackson K MukonzoEleni Aklillu
Oct 20, 2011·Pharmacogenomics·Kerry Reed, Amadeo M Parissenti
Jan 2, 2014·Omics : a Journal of Integrative Biology·Eleni AklilluMagnus Ingelman-Sundberg
Jun 19, 2014·Expert Opinion on Drug Metabolism & Toxicology·Pablo BarreiroVincent Soriano
Nov 24, 2012·Journal of Pharmaceutical Sciences·Rodrigo CristofolettiJennifer B Dressman
Nov 26, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Gianluca RussoLars Lennart Gustafsson
Mar 15, 2011·British Journal of Clinical Pharmacology·Dinko RekićMichael Ashton
Oct 22, 2013·Journal of Clinical Pharmacology·A M AbdelhadyB R Overholser
Jan 23, 2015·British Journal of Clinical Pharmacology·Phumla Z SinxadiDavid W Haas
Aug 8, 2015·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Giacomo Maria PaganottiVincenzo Vullo
Mar 19, 2016·British Journal of Clinical Pharmacology·Andrzej BienczakPaolo Denti
Sep 20, 2016·Clinical Pharmacokinetics·Andrea CalcagnoStefano Bonora
Oct 26, 2016·AIDS Research and Treatment·Jacinta Nwamaka NwoguBabafemi Taiwo
Oct 26, 2016·The Pharmacogenomics Journal·J L BakerC N Rotimi
May 19, 2018·Expert Opinion on Drug Metabolism & Toxicology·Gabriel StillemansLaure Elens

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.