Fukuhara S, Echizen H, Naito M, Ishikawa S, Toyama M, Nagoshi H, Honda M, Ishizaki T
Department of Medicine, Second National Hospital of Tokyo, Division of Clinical Pharmacology, Japan.
J Clin Pharmacol. 1989 Feb;29(2):102-6. doi: 10.1002/j.1552-4604.1989.tb03294.x.
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 less than 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.