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P-glycoprotein function in the elderly

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The MDR1-encoded P-glycoprotein (Pgp) represents the best-studied membraneous efflux pump defending the body against xenobiotics. Various polymorphisms (single nucleotide polymorphisms; SNPs) in the MDR1 gene have been identified, and a silent mutation in exon 26 (C3435T) has been correlated with duodenal expression of Pgp, which might affect the disposition of certain drugs. The C3435T SNP has been shown to be linked to another SNP (G2677T/A) in exon 21 which leads to an amino acid exchange. So far, the influence of age on Pgp function has been neglected. As the function of Pgp might be altered in advanced age, we investigated in groups of fit and frail elderly subjects whether the efflux of the Pgp-probe rhodamine 123 from CD56+ natural killer cells was age dependent and whether it was affected by the two SNPs.

Methods

Leukocytes were isolated from blood of 18 healthy elderly subjects (mean age 69 years) and 20 geriatric frail patients (mean age 78 years) and data compared with 21 previously studied young healthy Caucasian individuals (mean age 33 years). Subjects were homozygous for either CC- or TT-genotype (SNP C3435T) and additionally differentiated according to genotype GG or TT of the SNP G2677T. Using flow cytometry, rhodamine fluorescence was monitored in CD56+ cells.

Results

In contrast to the young controls, in both elderly populations no significant difference between the CC and TT genotypes (exon 26) could be observed in rhodamine fluorescence. Furthermore, only for the TT genotype (exon 26) did frail elderly demonstrate some reduced Pgp function (P=0.03) if compared with the young healthy subjects. If the three groups were compared independent of the genotype, no age effects were observed. For all assessed genotypes, there was no significant difference between fit and frail elderly subjects.

Conclusion

Aging and frailty have apparently only a minor impact on this validated cellular Pgp model and it could be assumed that function of Pgp is quite well preserved in patients of advanced age.

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Acknowledgements

We appreciate the valuable support of Drs. E. Schaeffeler and M. Schwab for the genotyping procedures. We thank Drs M. Hitzl and M. Fromm for helpful discussions and Mrs. A. Zwicker and Mrs. S. Kubitsch for technical assistance. This work was supported by the Robert Bosch Foundation Stuttgart, Germany. The present study complies with the current laws of Germany.

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  1. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 , Stuttgart, Germany

    Stefanie S. Brenner & Ulrich Klotz

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  1. Stefanie S. Brenner
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  2. Ulrich Klotz
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Correspondence to Ulrich Klotz.

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Brenner, S.S., Klotz, U. P-glycoprotein function in the elderly. Eur J Clin Pharmacol 60, 97–102 (2004). https://doi.org/10.1007/s00228-004-0733-4

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