Related Experiment Videos
Relationship of CYP2D6, CYP3A, POR, and ABCB1 genotypes with galantamine plasma concentrations
Muriel Noetzli1, Monia Guidi, Karsten Ebbing
1Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, University Hospital Lausanne, Prilly-Lausanne, Switzerland.
Background:
The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations.
Methods:
In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined.
Results:
The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL · mg, P = 0.025, and 1.8 ng/mL · mg, P = 0.004), respectively.
Conclusions:
The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.
Related Concept Videos
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism