RELATIONSHIP OF CHANGES IN FELODIPINE PHARMACOKINETICS TO HEMODYNAMICS DURING CHRONIC ORAL TREATMENT OF CONGESTIVE-HEART-FAILURE PATIENTS

In congestive heart failure patients the kinetics of felodipine, a dih ydropyridine calcium antagonist, show interpatient differences after a cute i.v. administration that disappear after 8 weeks oral treatment w ith a change in kinetics in the patients with the largest clearances ( CL) and the smallest volumes of distribution (V-ss) Pharmacokinetic an d haemodynamic data were combined to construct a haemodynamic-pharmaco kinetic model. This model shows that the differences between the patie nts in i.v. pharmacokinetics are consistent with a difference in plasm a flow distribution between liver and poorly perfused tissues. In pati ents in whom kinetics changed, felodipine treatment is supposed to cau se a redistribution of flow from liver to peripheral tissues: accompan ied by a decreased work load of the heart and a larger increase in VO2 max during therapy than in the other patients, whose workload increase d. This suggests a better therapeutic response in the patients whose k inetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might b e predictive for the therapeutic effect of felodipine.