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

被引：20

作者：

Noetzli, Muriel ^{[1
]}

Guidi, Monia ^{[2
,3
]}

Ebbing, Karsten ^{[4
]}

Eyer, Stephan ^{[5
]}

Zumbach, Serge ^{[6
]}

Giannakopoulos, Panteleimon ^{[7
]}

von Gunten, Armin ^{[4
]}

Csajka, Chantal ^{[2
,3
]}

Eap, Chin B. ^{[1
,3
]}

机构：

[1] Univ Lausanne Hosp, Dept Psychiat, Ctr Psychiat Neurosci, Unit Pharmacogenet & Clin Psychopharmacol, Prilly, Switzerland

[2] Univ Lausanne Hosp, Dept Med, Div Clin Pharmacol, Lausanne, Switzerland

[3] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, Geneva, Switzerland

[4] Univ Lausanne Hosp, Dept Psychiat, Serv Old Age Psychiat, Prilly, Switzerland

[5] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland

[6] Cantonal Hosp Fribourg, Dept Psychiat, Fribourg Mental Hlth Network, Marsens, Switzerland

[7] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Div Gen Psychiat, Geneva, Switzerland

来源：

THERAPEUTIC DRUG MONITORING | 2013年 / 35卷 / 02期

关键词：

galantamine; CYP2D6; ABCB1; CYP3A; pharmacogenetics; ALZHEIMERS-DISEASE; CYTOCHROME-P450; 2D6; PHARMACOKINETICS; PHARMACOGENETICS; PERFORMANCE; GUIDELINES; MEDICATION; HUMANS; UPDATE;

D O I：

10.1097/FTD.0b013e318282ff02

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

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.

引用

页码：270 / 275

页数：6

共 29 条

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