The interactions between nisoldipine and two beta‐adrenoceptor antagonists‐atenolol and propranolol.

Abstract

1. The interactions between the dihydropyridine calcium antagonist nisoldipine and two beta‐adrenoceptor blocker drugs (atenolol and propranolol) were investigated in two groups of healthy normotensive subjects. 2. The steady state plasma concentrations of both beta‐ adrenoceptor blockers were significantly altered by the addition of nisoldipine: for propranolol there were significant increases in Cmax, by about 50%, and in AUC by about 30% and for atenolol there was a significant increase in Cmax, by about 20%. 3. The addition of nisoldipine was also associated with significant changes in apparent liver blood flow (measured by indocyanine green clearance) from 1.4 to 2.4 l min‐1 in the atenolol group and from 1.3 to 2.3 l min‐1 in the propranolol group. 4. Both nisoldipine‐beta‐adrenoceptor blocker combinations were associated with small enhanced blood pressure reductions e.g. from 104/60 with atenolol alone to 98/50 mm Hg with the combination but there was no alteration to the extent of beta‐ adrenoceptor blockade (as assessed by bicycle ergometry). 5. This pharmacodynamic profile in healthy normotensives is consistent with the known therapeutic efficacy of such combination treatments in patients with hypertension and angina. 6. It is suggested that there is a pharmacokinetic component to the efficacy of this type of combination, perhaps reflecting vasodilator‐induced changes in drug absorption and/or hepatic extraction.

Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats

“…It has been reported that there is a little pharmacokinetic interaction between -blocking agents and dihydropyridine Ca-channel blockers (Smith et al 1987;Elliot et al 1991). In this experiment, the results showed that the plasma carvedilol concentrations and AUC 0 !…”

Calcium Antagonists

“…Pharmacokinetic changes were seen with the combinations of atenolol and nitrendipine, [31] and atenolol with nisoldipinePO] Pharmacokinetic changes were more marked with a combination of propranolol and nisoldipine than atenolol and nisoldipine. [30] Coadministration of oral verapamil with oral atenolol [33] resulted in a variable increase in atenolol steady-state plasma concentrations in a group of patients receiving long term maintenance therapy with these 2 agents. The observed prolongation of the PR interval, however, is likely to contribute to intolerance of the combination of atenolol and verapamil in individuals.…”