Study on the interaction of the dopamine agonist alpha-dihydroergocryptine with the pharmacokinetics of digoxin
| Autor: | C. de Mey, A. Retzow, B Vens-Cappell, D Mazur, Monika Althaus |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Digoxin Adolescent Blood Pressure Dihydroergotoxine Pharmacology Pharmacokinetics Oral administration Drug Discovery medicine Humans Drug Interactions Cross-Over Studies business.industry Venous blood Drug interaction Middle Aged Crossover study Tolerability Concomitant Area Under Curve Dopamine Agonists business medicine.drug Half-Life |
| Zdroj: | Arzneimittel-Forschung. 50(7) |
| ISSN: | 0004-4172 |
| Popis: | Aim: The study was carried out to explore the potential for pharmacokinetic interaction of a single oral dose of alpha-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid(R)) with digoxin. Methods: The serum pharmacokinetics of digoxin were analysed after the administration of single oral doses of 0.5 mg digoxin administered either alone or concomitantly with 20 mg DHEC according to a randomised, non-blinded, two-period cross-over design, with study periods 2 weeks apart. Twelve healthy male subjects, 23 to 39 years of age were enrolled and were investigated in accordance with the protocol. Venous blood was sampled up to 48 h after dosing. Concentrations of digoxin in serum were determined by a competitive radioimmunoassay. Results. The mean C-max were 1.97 +/- 0.87 (after a median t(max) of 1 h) and 2.05 +/- 0.95 ng/ml (after a median t(max) of 0.83 h) after the administration of digoxin with (test) and without (reference) concomitant DHEC, respectively; the corresponding estimated treatment ratio for test: reference was 0.939, 95 % CI: 0.781 to 1.129. The mean AUC((0-48)) were 13.6 +/- 5.0 ng . h/ml and 13.3 +/- 4.7 ng . h/ml for the test and reference treatment, respectively; the corresponding estimated treatment ratio for test: reference was 1.011, 95 % CI: 0.866 to 1.142. In addition, no clinically significant changes were observed by ECG monitoring. The tolerability of digoxin alone was good, significantly more adverse events occurred when co-administered with DHEC; these corresponded with the known adverse reaction profile and were of moderte intensity. No premature study termination was thus necessary. Conclusion: The present study did not demonstrate clinically relevant interaction of a single dose of DHEC on the pharmacokinetics of digoxin. On the basis of these observations there is no indication for an a priori adjustment of the dose of digoxin when concomitant treatment with DHEC is initiated. |
| Databáze: | OpenAIRE |
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