Phenoconversion of CYP2C9 in epilepsy limits the predictive value of CYP2C9 genotype in optimizing valproate therapy

Personalized Medicine
Katalin TóthKatalin Monostory

Abstract

Since prominent role in valproate metabolism is assigned to CYP2C9 in pediatric patients, the association between children's CYP2C9-status and serum valproate concentrations or dose-requirements was evaluated. The contribution of CYP2C9 genotype and CYP2C9 expression in children (n = 50, Caucasian) with epilepsy to valproate pharmacokinetics was analyzed. Valproate concentrations were significantly lower in normal expressers with CYP2C9*1/*1 than in low expressers or in patients carrying polymorphic CYP2C9 alleles. Consistently, the dose-requirement was substantially higher in normal expressers carrying CYP2C9*1/*1 (33.3 mg/kg vs 13.8-17.8 mg/kg, p < 0.0001). Low CYP2C9 expression significantly increased the ratio of poor metabolizers predictable from CYP2C9 genotype (by 46%). Due to the substantial downregulation of CYP2C9 expression in epilepsy, inferring patients' valproate metabolizing phenotype merely from CYP2C9 genotype results in false prediction.

References

Jan 1, 1995·Pharmacology & Therapeutics·B Fromenty, D Pessayre
Oct 23, 1997·Clinical Pharmacology and Therapeutics·W M O'NeilI W Wainer
Sep 14, 2001·Journal of Internal Medicine·M Ingelman-Sundberg
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·D Gail McCarver, Ronald N Hines
Jan 7, 2004·Drug Metabolism Reviews·Jean Marc PascussiMarie José Vilarem
Mar 30, 2004·Archives of Biochemistry and Biophysics·Kayo SakaguchiChristopher King
Sep 17, 2005·Journal of Clinical Pharmacy and Therapeutics·G M Peterson, M Naunton
Apr 13, 2006·Paediatric Drugs·Renzo Guerrini
Sep 2, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tony K L KiangThomas K H Chang
Jun 20, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Alison E Aitken, Edward T Morgan
Apr 9, 2008·Journal of Inherited Metabolic Disease·M F B SilvaI Tavares de Almeida
Aug 13, 2008·Analytical and Bioanalytical Chemistry·Ulrich M ZangerMatthias Schwab
Oct 16, 2008·British Journal of Cancer·N A HelsbyM Findlay
Jan 20, 2010·European Journal of Clinical Pharmacology·Amanda E JonesAngela D M Kashuba
Jul 7, 2010·Toxicology Mechanisms and Methods·Noushin Amini-ShiraziAbbas Kebriaeezadeh
Aug 28, 2010·Journal of Biomedicine & Biotechnology·Sébastien ChateauvieuxMarc Diederich
Jun 15, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shouhong GaoWansheng Chen
Jan 21, 2012·The Journal of Pharmacology and Experimental Therapeutics·Manna TemesváriKatalin Monostory
Feb 15, 2013·Pharmacogenetics and Genomics·Yogita Ghodke-PuranikTeri E Klein
Apr 10, 2013·Seizure : the Journal of the British Epilepsy Association·Irem Fatma UludagGuldal Kirkali
Jun 25, 2013·Clinical Biochemistry·Radu M Nanau, Manuela G Neuman
Jun 11, 2014·British Journal of Clinical Pharmacology·Rashmi R Shah, Robert L Smith

❮ Previous
Next ❯

Citations

Nov 10, 2017·Current Neuropharmacology·Katalin MonostoryGábor Csukly
Apr 18, 2018·Pharmacological Reports : PR·Ádám Ferenc KissKatalin Monostory
May 15, 2015·Epilepsia·Tamás BűdiKatalin Monostory
Jan 19, 2016·Pharmacogenomics·Rashmi R ShahRobert L Smith
Jul 9, 2020·Pharmacological Reports : PR·Máté Tamás DériKatalin Monostory

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

CYPtest

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.

Related Papers

Current Neuropharmacology
Katalin MonostoryGábor Csukly
The International Journal of Neuropsychopharmacology
Katalin TóthKatalin Monostory
The International Journal of Neuropsychopharmacology
Katalin TóthKatalin Monostory
© 2022 Meta ULC. All rights reserved