Oral bioavailability of digoxin is enhanced by talinolol: Evidence for involvement of intestinal P-glycoprotein

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Kristin Westphal - , University of Greifswald (Author)
  • Anita Weinbrenner - , University of Greifswald (Author)
  • Thomas Giessmann - , University of Greifswald (Author)
  • Marko Stuhr - , University of Greifswald (Author)
  • Gerd Franke - , University of Greifswald (Author)
  • Michael Zschiesche - , University of Greifswald (Author)
  • Reinhard Oertel - , Institute of Clinical Pharmacology, University Medicine (Faculty of Medicine and University Hospital), Division of Clinical Pharmacology, University of Greifswald (Author)
  • Bernd Terhaag - , University of Greifswald, Menarini-Von Heyden GmbH Dresden (Author)
  • Heyo K. Kroemer - , University of Greifswald (Author)
  • Werner Siegmund - , University of Greifswald (Author)

Abstract

Objective: Recent data indicated that disposition of oral digoxin is modulated by intestinal P-glycoprotein. The cardioselective β-blocker talinolol has been described to be secreted by way of P-glycoprotein into the lumen of the gastrointestinal tract after oral and intravenous administration. We therefore hypothesized that coadministration of digoxin and talinolol may lead to a drug-drug interaction based on a competition for intestinal P-glycoprotein. Methods: Pharmacokinetics of digoxin (0.5 mg orally), talinolol (30 mg intravenously and 100 mg orally), and digoxin plus talinolol orally, as well as digoxin plus talinolol intravenously, were assessed in five male and five female healthy volunteers (age range, 23 to 30 years; body weight, 60 to 95 kg) in a changeover study with at least a 7-day washout period. Digoxin and talinolol were analyzed by fluorescence polarization immunoassay and HPLC, respectively. Results: Oral coadministration of 100 mg talinolol increased the area under the concentration-time curve (AUC) from 0 to 6 hours and the AUC from 0 to 72 hours of digoxin significantly by 18% and 23%, respectively (5.85 ± 1.49 versus 7.22 ± 1.29 ng · h/mL and 23.0 ± 3.3 versus 27.1 ± 3.7 ng · h/mL, for both P < .05) and the maximum serum levels by 45%. Renal clearance and half-life of digoxin remained unchanged. Coinfusion of 30 mg talinolol with oral digoxin had no significant effects on digoxin pharmacokinetics. Digoxin did not affect the disposition of talinolol after both oral and intravenous administration. Conclusion: We observed a significantly increased bioavailability of digoxin with oral coadministration of talinolol, which is most likely caused by competition for intestinal P-glycoprotein.

Details

Original languageEnglish
Pages (from-to)6-12
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume68
Issue number1
Publication statusPublished - 2000
Peer-reviewedYes

External IDs

PubMed 10945310
ORCID /0000-0003-1526-997X/work/142247265

Keywords

ASJC Scopus subject areas