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); on.y 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. We differences between the effects of oral and intravenous
verapamil on atrioventricular conduction may be the result of stereoselective hepatic inactivation of
verapamil's I-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.