Nifedipine kinetics and dynamics during rectal infusion to steady state with an osmotic system.

Nifedipine steady-state kinetics and dynamics were investigated in a placebo-controlled study of six healthy subjects. Nifedipine was given rectally through an osmotic system at a zero-order rate for 24 hr. Steady-state plasma concentrations of approximately 20 ng/ml were achieved within 6 to 8 hr. Nifedipine lowered diastolic blood pressure (DBP) and increased forearm blood flow (FBF) and plasma norepinephrine concentration. On the other hand, heart rate (HR) and systolic blood pressure were not affected. Changes in DBP and FBF were closely related to nifedipine plasma concentrations during and immediately after the infusion period. Our data indicate that nifedipine lowers blood pressure in subjects with normotension and that it is possible by infusing the drug at a relatively low rate to dissociate its effect on blood pressure from that on HR.