PHARMACOGENETICS The association of ABCB1 polymorphisms and elevated serum digitoxin concentrations in geriatric patients Charalampos Dragonas & Jan T. Wagner & Hans J. Heppner & Thomas Bertsch & Wolfgang Muhlberg & Susanne Wicklein & Andreas Pahl & Christine Diewald & Iouri Bachmakov & Cornel C. Sieber & Martin F. Fromm Received: 10 June 2007 / Accepted: 14 November 2007 / Published online: 16 December 2007 # Springer-Verlag 2007 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·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. Conclusion In this sample of frail geriatric patients, the impact of ABCB1 C3435T genotype on serum digitoxin concentration was not of major relevance. Regular moni- toring of digitoxin blood levels and surveillance of appropriate drug use remain the best ways to prevent digitoxin intoxications in the elderly. Keywords Digitoxin . ABCB1 . Polymorphism . P-glycoprotein . Geriatric Introduction Due to the high prevalence of supraventricular tachyar- rhythmias and cardiac failure in higher age groups, digitalis glycosides are among the most commonly prescribed drugs among the older population [1–3]. Given its narrow therapeutic range, the potential toxicity of digitalis in this population is of high clinical relevance [4–6]. Generally, the drug safety of digitoxin is regarded as superior to digoxin for those of advanced age. It is argued that since digoxin is predominantly eliminated via the kidneys, the risk of intoxication increases with a decline in renal function, which is commonly observed during the aging process [4, 7]. In fact, a recent study reported three times higher toxicity rates for elderly patients taking digoxin than for patients taking digitoxin [8]. However, digitoxin Eur J Clin Pharmacol (2008) 64:367–372 DOI 10.1007/s00228-007-0418-x DO00418; No of Pages C. Dragonas (*) : J. T. Wagner : H. J. Heppner : W. Muhlberg : S. Wicklein : C. Diewald : C. C. Sieber Institute for Biomedicine of Aging, Department of Internal Medicine V (Geriatrics), University of Erlangen-Nuremberg, Nuremberg, Germany e-mail: c.dragonas@gmx.net T. Bertsch Institute of Clinical Chemistry and Laboratory Medicine, Klinikum Nuremberg, Nuremberg, Germany A. Pahl : I. Bachmakov : M. F. Fromm Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany