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

Dragonas C, Wagner J, Heppner HJ, Bertsch T, Mühlberg W, Wicklein S, Pahl A, Bachmakov I, Sieber C, Fromm M (2008)

Publication Status: Published

Publication Type: Journal article

Publication year: 2008

Journal

European Journal of Clinical Pharmacology Springer Verlag (Germany)

Publisher: SPRINGER

Book Volume: 64

Pages Range: 367-372

Journal Issue: 4

DOI: 10.1007/s00228-007-0418-x

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.

Authors with CRIS profile

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

Involved external institutions

Klinikum Nürnberg DE Germany (DE)

How to cite

APA:

Dragonas, C., Wagner, J., Heppner, H.J., Bertsch, T., Mühlberg, W., Wicklein, S.,... Fromm, M. (2008). The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients. European Journal of Clinical Pharmacology, 64(4), 367-372. https://dx.doi.org/10.1007/s00228-007-0418-x

MLA:

Dragonas, Charalampos, et al. "The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients." European Journal of Clinical Pharmacology 64.4 (2008): 367-372.

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