Relationship of CYP2D6, CYP3A, POR, and ABCB1 Genotypes With Galantamine Plasma Concentrations

• DOI: 10.1097/ftd.0b013e318282ff02
• Publication Date: 2013-03-22T21:42:25Z
• Authors: Muriel Noetzli; Monia Guidi; Karsten Ebbing; Stephan Eyer; Serge Zumbach; Panteleimon Giann...; Armin von Gunten; Chantal Csajka; Chin B. Eap
• Keywords: Aged, 80 and over; Male; ATP Binding Cassette Transporter, Subfamily B; Genotype; Galantamine; 3. Good health; Cohort Studies; 03 medical and health sciences; Cross-Sectional Studies; 0302 clinical medicine; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Humans; Dementia; Female; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cholinesterase Inhibitors; Aged; NADPH-Ferrihemoprotein Reductase

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.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.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.The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.