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Relationship of changes in felodipine pharmacokinetics to haemodynamics during chronic oral treatment of congestive heart failure patients

โœ Scribed by A. H. J. Scaf; H. Wesseling; P. H. J. M. Dunselman


Publisher
Springer
Year
1995
Tongue
English
Weight
795 KB
Volume
49
Category
Article
ISSN
0031-6970

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โœฆ Synopsis


In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (Vss). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine. Key words Felodipine; pharmacokinetics, haemodynamics, congestive heart failure A major part of clinical drug research is designed to compare pharmacotherapeutic regimens. In most cases the aim is to prove that the new regimen is superior to the old one or to placebo. In such studies aggregated results obtained with the respective regimens are com-


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