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01.12.2007 | Original Research Article

Role of P-Glycoprotein Inhibition for Drug Interactions

Evidence from In Vitro and Pharmacoepidemiological Studies

verfasst von: Sonja Eberl, Bertold Renner, Antje Neubert, Mareike Reisig, Iouri Bachmakov, Jörg König, Frank Dörje, Thomas E. Mürdter, Andreas Ackermann, Harald Dormann, Karl G. Gassmann, Eckhart G. Hahn, Stefanie Zierhut, Kay Brune, Prof. Martin F. Fromm

Erschienen in: Clinical Pharmacokinetics | Ausgabe 12/2007

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Abstract

Objectives

We determined in vitro the potency of macrolides as P-glycoprotein inhibitors and tested in hospitalised patients whether coadministration of P-glycoprotein inhibitors leads to increased serum concentrations of the P-glycoprotein substrates digoxin and digitoxin.

Methods

In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transport was investigated in Caco-2 cells. In a pharmacoepidemiological study, we analysed the serum digoxin and digitoxin concentrations with and without coadministration of P-glycoprotein inhibitors in hospitalised patients.

Results

All macrolides inhibited P-glycoprotein-mediated digoxin transport, with concentrations producing 50% inhibition (IC₅₀) values of 1.8, 4.1, 15.4, 21.8 and 22.7 μmol/L for telithromycin, clarithromycin, roxithromycin, azithromycin and erythromycin, respectively. Coadministration of P-glycoprotein inhibitors was associated with increased serum concentrations of digoxin (1.3 ± 0.6 vs 0.9 ± 0.5 ng/mL, p < 0.01). Moreover, patients receiving macrolides had higher serum concentrations of cardiac glycosides (p < 0.05).

Conclusion

Macrolides are potent inhibitors of P-glycoprotein. Drug interactions between P-glycoprotein inhibitors and substrates are likely to occur during hospitalisation.

The use of trade names is for product identification purposes only and does not imply endorsement.

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Titel: Role of P-Glycoprotein Inhibition for Drug Interactions
Evidence from In Vitro and Pharmacoepidemiological Studies
verfasst von: Sonja Eberl
Bertold Renner
Antje Neubert
Mareike Reisig
Iouri Bachmakov
Jörg König
Frank Dörje
Thomas E. Mürdter
Andreas Ackermann
Harald Dormann
Karl G. Gassmann
Eckhart G. Hahn
Stefanie Zierhut
Kay Brune
Prof. Martin F. Fromm
Publikationsdatum: 01.12.2007
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 12/2007
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200746120-00004

Springer Medizin

Abstract

Objectives

Methods

Results

Conclusion

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