Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein
| Autor: | Werner Siegmund, Zschiesche M, Thomas Giessmann, Heyo K. Kroemer, Bernd Terhaag, Marko Stuhr, Reinhard Oertel, G. Franke, Kristin Westphal, Anita Weinbrenner |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Digoxin Cardiotonic Agents Time Factors Adrenergic beta-Antagonists Administration Oral Biological Availability Pharmacology Propanolamines chemistry.chemical_compound Pharmacokinetics Oral administration Reference Values Fluorescence Polarization Immunoassay medicine Humans Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 Infusions Intravenous Chromatography High Pressure Liquid Gastrointestinal tract Cross-Over Studies Chemistry Antagonist Drug interaction Bioavailability Intestinal Absorption Area Under Curve Drug Therapy Combination Female Talinolol medicine.drug Half-Life |
| Zdroj: | Clinical pharmacology and therapeutics. 68(1) |
| ISSN: | 0009-9236 |
| Popis: | 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. Clinical Pharmacology & Therapeutics (2000) 68, 6–12; doi: 10.1067/mcp.2000.107579 |
| Databáze: | OpenAIRE |
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