Study on the interaction of the dopamine agonist alpha-dihydroergocryptine with the pharmacokinetics of digoxin.
OBJECTIVE
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) 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 Cmax were 1.97 +/- 0.87 (after a median tmax of 1 h) and 2.05 +/- 0.95 ng/ml (after a median tmax 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 moderate intensity. No premature study termination was thus necessary.


CONCLUSIONS
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.
Retzow
A
A
Desitin Arzneimittel GmbH, Hamburg, Germany.
Althaus
M
M
de Mey
C
C
Mazur
D
D
Vens-Cappell
B
B
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D004088:Dihydroergotoxine / Q000009:adverse effects / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged
D018491:Dopamine Agonists; D004088:Dihydroergotoxine; D004077:Digoxin