Eberl, Sonja and Renner, Bertold and Neubert, Antje and Reisig, Mareike and Bachmakov, Iouri and Koenig, Joerg and Doerje, Frank and Muerdter, Thomas E. and Ackermann, Andreas and Dormann, Harald and Gassmann, Karl G. and Hahn, Eckhart G. and Zierhut, Stefanie and Brune, Kay and Fromm, Martin F. (2007) Role of P-glycoprotein inhibition for drug interactions: Evidence from in vitro and pharmacoepidemiological studies. CLINICAL PHARMACOKINETICS, 46 (12). pp. 1039-1049. ISSN 0312-5963,
Full text not available from this repository. (Request a copy)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 mu mol/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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCED DIGOXIN TOXICITY; ORAL BIOAVAILABILITY; HEART-FAILURE; CLARITHROMYCIN; DIGITOXIN; TRANSPORT; QUINIDINE; ROXITHROMYCIN; TELITHROMYCIN; INTOXICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Jan 2021 13:18 |
| Last Modified: | 11 Jan 2021 13:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33381 |
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