An interindividual variability in the sensitivity of atrioventricular node to diltiazem in patients with paroxysmal supraventricular tachycardia

To study the sensitivity of atrioventricular (AV) node to diltiazem in seven patients with paroxysmal supraventricular tachycardia (PSVT), we analyzed the plasma concentration-response relationship of this Ca-antagonist using AH interval as an index for assessing its Ca channel blocking effect on the AV node after an IV infusion (0.4 mg/kg). The postdose AH intervals were prolonged compared with the baseline, and their percentage changes correlated significantly (P < 0.01) with log-diltiazem concentrations in all patients. However, drug concentrations associated with a 20% prolongation of AH interval differed considerably among the patients (range; 65 to 260 ng/ml), indicating a large interindividual variability in the sensitivity of AV node to diltiazem. These results suggest that the interindividual difference in the responsiveness of AV node to diltiazem-induced Ca channel blocking effect may be one of the possible explanations for the therapeutic failure of this Ca-antagonist for terminating PSVT or preventing its recurrences in certain patients.