Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies
| Autor: | Martin F. Fromm, Mareike Reisig, Jörg König, Harald Dormann, Bertold Renner, Thomas E. Mürdter, Karl G Gassmann, Frank Dörje, Andreas Ackermann, S. Zierhut, Sonja Eberl, Antje Neubert, Eckhart G. Hahn, Iouri Bachmakov, Kay Brune |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Digoxin Ketolides Heart Diseases Digitoxin Telithromycin Pharmacology Clarithromycin polycyclic compounds medicine Potency Humans Pharmacology (medical) Drug Interactions ATP Binding Cassette Transporter Subfamily B Member 1 Aspartate Aminotransferases IC50 Aged Aged 80 and over Inpatients Chemistry Roxithromycin Pharmacoepidemiology Inulin Alanine Transaminase Bilirubin Biological Transport Drug interaction Erythromycin Creatinine Female Macrolides Caco-2 Cells medicine.drug |
| Zdroj: | Clinical pharmacokinetics. 46(12) |
| ISSN: | 0312-5963 |
| Popis: | 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. 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. 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). Macrolides are potent inhibitors of P-glycoprotein. Drug interactions between P-glycoprotein inhibitors and substrates are likely to occur during hospitalisation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink