• Charalampos Dragonas, Jan T Wagner, Hans J Heppner, Thomas Bertsch, Wolfgang Muhlberg, Susanne Wicklein, Andreas Pahl, Christine Diewald, Iouri Bachmakov, Cornel C Sieber, and Martin F Fromm.
• Institute for Biomedicine of Aging, Department of Internal Medicine V (Geriatrics), University of Erlangen-Nuremberg, Nuremberg, Germany. c.dragonas@gmx.net
• Eur. J. Clin. Pharmacol. 2008 Apr 1;64(4):367-72.

ObjectiveDigitoxin 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.MethodsThe 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.ResultsAmong 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.l(-1) (95% CI 4.3-6.1) for the TT, 6.1 kg.l(-1) (95% CI 4.7-7.5) for the CT, and 6.2 kg.l(-1) (95% CI 4.6-7.7) for the CC genotype.ConclusionIn 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.

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