Influence of input rates on (±)-isradipine haemodynamics and concentration-effect relationship in healthy volunteers

Summary

Since the magnitude of the response to a drug may depend upon the drug input rate, the concentration-effect relationship of the new dihydropyridine (±)-isradipine was investigated using different administration modalities.

Ten normotensive healthy volunteers were given, double-blind and in a crossover fashion, isradipine as a 1 mg iv infusion, 5 mg oral solution, 5 mg standard tablet, 10 mg slow release formulation, and a placebo. Blood pressure, heart rate, and plasma isradipine concentrations were recorded for 24 h.

The maximal fall in diastolic blood pressure was similar after the infusion (-11.40 mmHg), the oral solution (-15.20 mmHg), and the standard tablet (-12.50 mmHg). In healthy volunteers the slow release form had no significant effect on blood pressure. The concentration-effect plots showed an increasing slope in the order infusion, solution, and tablet, and anticlockwise hysteresis. This was partly due to marked heart rate counter-regulation, the corresponding mean maximal heart rate increases being 24, 19, and 17 beats·min⁻¹.

The pronounced counter-regulation of the heart rate implies that a slow isradipine input rate would be more effective in decreasing blood pressure.