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


CONCLUSIONS
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.
Dragonas
Charalampos
C
Institute for Biomedicine of Aging, Department of Internal Medicine V (Geriatrics), University of Erlangen-Nuremberg, Nuremberg, Germany. c.dragonas@gmx.net
Wagner
Jan T
JT
Heppner
Hans J
HJ
Bertsch
Thomas
T
Muhlberg
Wolfgang
W
Wicklein
Susanne
S
Pahl
Andreas
A
Diewald
Christine
C
Bachmakov
Iouri
I
Sieber
Cornel C
CC
Fromm
Martin F
MF
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000704:Analysis of Variance; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood*; D004074:Digitoxin / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002316:Cardiotonic Agents; D004074:Digitoxin