EFFECTS OF HEMODYNAMIC-CHANGES ON THE ELIMINATION KINETICS OF VERAPAMIL AND NIFEDIPINE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (2) , 301-305
Abstract
This study used a steady-state approach to evaluate the relationships between the pharmacodynamic and pharmacokinetic characteristics of nifedipine and verapamil. In anesthesized and istrumented dogs, i.v. bolus/infusion dosing regiment were used for each drug to achieve and maintain stable drug concentrations in 4 different ranges rapidly. For both compounds, increases in doses were associated with disproportionate higher plasma drug concentrations, greater hemodynamic effects and significant reductions in systemic drug clearance. Progressive increases in the dose of nifedipine produced reductions in arterial pressure and reflex augmentation in cardiac output, together with decreases in calculated hepatic plasma flow which closely paralleled the decline in mean aortic pressure. Increasing doses of verapamil also resulted in decreased hepatic plasma flow, which was associated with both systemic hypotension and drug-induced decreases in cardiac output. The hemodynamic effects of both nifedipine and verapamil apparently result in changes in hepatic plasms flow which, in turn, result in significant alterations in systemic drug clearance. In this experimental model, the calculated hepatic plasma flow and observed systemic clearance values for the nifedipine and verapamil were closely related to concentrations of the respective drugs in plasma.

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