1.
Cicloprolol is a partial beta 1-adrenoceptor agonist considered for the treatment of patients with
coronary artery disease and impaired left ventricular function. In such patients,
digoxin remains in widespread use. 2. We assessed the pharmacokinetic and pharmacodynamic interaction between oral
cicloprolol 50 mg day-1 and oral
digoxin 0.25 mg day-1 in 10 healthy male volunteers, using a double-blind, randomised protocol, during three 8 day periods.
Digoxin was given alone during the first period to reach steady state; then
digoxin was given with
cicloprolol or placebo during the second and third periods, according to a cross-over design. 3. No significant adverse effects were observed. 4. The pharmacokinetics of
digoxin were not different significantly at the end of the placebo-
digoxin and
cicloprolol-
digoxin periods. 5. A significant increase in minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter recordings, was observed at the end of the
cicloprolol-
digoxin period as compared with the placebo-
digoxin period (means +/- s.e. mean, 57.1 +/- 3.2 beats min-1 vs 52.2 +/- 3.1 beats min-1, P less than 0.01; and 65.6 +/- 3.8 beats min-1 vs 59.9 +/- 3.9 beats min-1, P less than 0.01, respectively). 6. A significant increase in left ventricular ejection fraction and shortening fraction, assessed by echocardiography, was noted at the end of the
cicloprolol-
digoxin period as compared with the placebo-
digoxin period (means +/- s.e. mean, 66.4 +/- 1.4% vs 61.3 +/- 1.2%, P less than 0.05; and 37.0 +/- 1.1% vs 33.3 +/- 0.9%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)