Clinical relevance of verapamil plasma levels in stable angina pectoris

Plasma levels of verapamil and norverapamil were evaluated in 77 patients who received oral verapamil for treatment of angina pectoris. There was a sixfold interpatient variation in verapamil plasma concentrations, but plasma concentrations were linearly related to doses of the drug (240 to 480 mg/day) in the same patient (r = 0.81). Plasma concentrations of norverapamil, the major active metabolite of verapamil, were similar to those of verapamil. Although verapamil produced a significant improvement in exercise tolerance in most patients, the increase in exercise time was not related to plasma levels of the drug; however, most patients with improvement had plasma levels exceeding 100 ng/ml. An increase in the dose of verapamil from 320 to 480 mg daily produced a substantial (71 %) increase in plasma levels of the drug but no significant increase in exercise tolerance (4%). The average increase in the P-R interval with 480 mg of verapamil in these 77 patients was small (8%) (161 ± 18 to 174 ± 22 ms); only six patients had first-degree heart block. These minor effects on atrioventricular conduction were noted despite plasma verapamil concentrations in 76 patients that exceeded 100 ng/ml, a level that successfully converts supraventricular tachycardias after intravenous drug administration. The differences between the effects of oral and intravenous verapamil on atrioventricular conduction may be the result of stereoselective hepatic inactivation of verapamil's /-isomer. Determination of plasma levels of verapamil is of limited value in the management of patients with angina pectoris, but may be useful in the identification of nonresponders with plasma levels less than 100 ng/ml who may benefit from a further increment in drug dose.