Correlation of Plasma Levels of Nifedipine and Cardiovascular Effects After Sublingual Dosing in Normal Subjects

Only limited work has been reported about the relationships of cardiovascular effects and plasma concentrations of the calcium-channel blocker nifedipine. In this study, placebo and nifedipine in 10−, 20−, 30−, and 40−mg doses were administered sublingually to ten normal subjects with at least three days between dosing periods. Blood pressure and heart rate were monitored every 30 minutes for two hours, and blood samples were taken after each measurement for determination of plasma nifedipine concentration by a sensitive and specific gas chromatographic method. Systolic blood pressure fell significantly (P < 0.05) although briefly after 10 mg, but the effect persisted with larger doses. Diastolic blood pressure fell significantly only after 30− or 40-mg dosing. Heart rate increased significantly after all doses of nifedipine with the effect lasting longer with higher doses. Systolic blood pressure measurements were significantly related to the log of the concurrently measured plasma nifedipine concentrations (r = −.82, P < 0.001). Diastolic blood pressure was also related to log nifedipine concentration (r = −.69, P < 0.01). Heart rate, too, was linearly related to the log of nifedipine plasma levels (r = .75, P < 0.001). These data indicate that the hemodynamic effects observed after acute nifedipine administration may be used to estimate whether or not significant quantities of the drug are being absorbed and that the intensity of the hemodynamic effects may, therefore, serve as a bioassay to evaluate the appearance of drug in plasma in therapeutic quantities.