Study on the interaction of the dopamine agonist alpha-dihydroergocryptinewith the pharmacokinetics of digoxin

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 o f digoxin were analysed after the administration of single oral doses of 0. 5 mg digoxin administered either alone or concomitantly with 20 mg DHEC acc ording to a randomised, non-blinded, two-period cross-over design, with stu dy periods 2 weeks apart. Twelve healthy male subjects, 23 to 39 years of a ge were enrolled and were investigated in accordance with the protocol. Ven ous 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) a nd 2.05 +/- 0.95 ng/ml (after a median t(max) of 0.83 h) after the administ ration of digoxin with (test) and without (reference) concomitant DHEC, res pectively; 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: referen ce was 1.011, 95 % CI: 0.866 to 1.142. In addition, no clinically significa nt changes were observed by ECG monitoring. The tolerability of digoxin alo ne was good, significantly more adverse events occurred when co-administere d with DHEC; these corresponded with the known adverse reaction profile and were of moderte intensity. No premature study termination was thus necessa ry. Conclusion: The present study did not demonstrate clinically relevant inter action 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 adjustme nt of the dose of digoxin when concomitant treatment with DHEC is initiated .