Serial M-mode echocardiography in evaluation of the cardiovascular effects of tiapamil and their relationship to plasma levels in patients with coronary heart disease.

Tiapamil (Ro 11-1781) is a new calcium antagonist. Several investigators have reported about its efficacy against cardiac arrhythmias and angina pectoris. However, there was no study that assessed a possible relationship between hemodynamic effects and plasma concentration. Our study was aimed to investigate any possible relationship between cardiovascular effects of tiapamil and its plasma concentration. We selected 8 coronary; patients (6 males and 2 females) with a mean age of 61.9 yr and a mean weight of 70.9 kg. Tiapamil was administered per os at the dose of 250 mg t.i.d. for 4 consecutive days. Hemodynamic data were obtained by means of echocardiography, ECG and sphygmomanometry. Plasma concentrations of Ro 11-1781 and its major metabolites were measured by means of high pressure liquid chromatography. With tiapamil, the morning systolic BP fell from 130.6 +/- 19.5 (mean +/- SD, pretreatment) to 114.4 +/- 18.2 mm Hg on day 4, the change being clinically and statistically significant (P less than 0.02 by paired t-tests). Diastolic BP and HR remained unchanged. LVEDD and LVESD were not affected to any relevant extent, but VCF was significantly (P less than 0.05) and persistently increased. Tiapamil was well absorbed, but large interindividual variations were observed. As a general rule, no direct relationship between plasma concentrations and hemodynamic effects could be demonstrated. However, the number of patients is too small to allow general conclusions. At the above dose, tiapamil did not elicit any clinically detectable negative inotropic or negative chronotropic effect, probably because of its lowering effect on systolic BP.