The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients

Journal article


Publication Details

Author(s): Dragonas C, Wagner J, Heppner HJ, Bertsch T, Mühlberg W, Wicklein S, Pahl A, Bachmakov I, Sieber C, Fromm M
Journal: European Journal of Clinical Pharmacology
Publisher: SPRINGER
Publication year: 2008
Volume: 64
Journal issue: 4
Pages range: 367-372
ISSN: 0031-6970


Abstract

Objective Digitoxin is a known substrate of the efflux pump P-glycoprotein (gene name: ABCB1). P-glycoprotein expression was shown to be modulated by single nucleotide polymorphisms in the ABCB1 gene, but it remains unclear whether these polymorphisms influence digitoxin blood levels. Our objective was to examine the association of ABCB1 C3435T genotype and elevated serum digitoxin concentrations (SDC) in a cohort of 77 geriatric patients consecutively admitted to a geriatric department over a 12-month period.Methods The impact of ABCB1 3435 CC, CT, and TT genotypes on SDC and SDC normalized for daily digitoxin dosage and body weight was assessed by multivariate regression analysis.Results Among participants, 18 (23%) had the CC, 36 (47%) the CT, and 23 (30%) the TT genotype. Adjusting for relevant covariates, no significant association of ABCB1 C3435T genotype and SDC or normalized SDC was detected. Mean SDC was 22.4 ng/ml (95% CI 18.9-25.9) for the TT, 21.8 ng/ml (95% CI 18.1-25.5) for the CT, and 25.7 ng/ml (95% CI 20.6-30.8) for the CC genotype. The means for normalized SDC were 5.2 kg center dot l(-1) (95% CI 4.3-6.1) for the TT, 6.1 kg center dot l(-1) (95% CI 4.7-7.5) for the CT, and 6.2 kg center dot l(-1) (95% CI 4.6-7.7) for the CC genotype.Conclusion In this sample of frail geriatric patients, the impact of ABCB1 C3435T genotype on serum digitoxin concentration was not of major relevance. Regular monitoring of digitoxin blood levels and surveillance of appropriate drug use remain the best ways to prevent digitoxin intoxications in the elderly.


FAU Authors / FAU Editors

Fromm, Martin Prof. Dr.
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie
Heppner, Hans Jürgen PD Dr.
Medizinische Fakultät
Mühlberg, Wolfgang PD Dr.
Medizinische Fakultät
Pahl, Andreas Prof. Dr.
Medizinische Fakultät
Sieber, Cornel Prof. Dr.
Lehrstuhl für Innere Medizin (Geriatrie)
Wagner, Jennifer
Professur für Computational Medicine (DFG-Forschungsprofessur)


External institutions with authors

Klinikum Nürnberg

Last updated on 2019-21-07 at 07:57