Myocardial Pharmacokinetics and Pharmacodynamics of Nifedipine in the Isolated Rabbit Heart
| Autor: | Folmer Nielsen-Kudsk, J. Askholt |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Nifedipine Pyridines In Vitro Techniques Pharmacology Toxicology Contractility Oxygen Consumption Pharmacokinetics Coronary Circulation medicine Animals Distribution (pharmacology) business.industry Myocardium Heart Myocardial Contraction Dipyridamole Kinetics Dromotropic Calcium Female Rabbits Steady state (chemistry) business Perfusion medicine.drug |
| Zdroj: | Acta Pharmacologica et Toxicologica. 48:330-339 |
| ISSN: | 0001-6683 |
| Popis: | The myocardial accumulation and disposition pharmacokinetics of the antianginal and antihypertensive calcium-antagonistic drug nifedipine were investigated in isolated, perfused and spontaneously beating rabbit hearts. The myocardium behaved pharmacokinetically as a two-compartment system with regard to the drug. The mean half-lives of the alpha-phase of distribution and of the beta-phase of disposition were about 1.2 and 6.5 min., respectively. Perfusion with a modified Krebs-Henseleit solution containing nifedipine in a concentration of 50 ng ml-1 caused by accumulation of about 1277 ng g-1 in the myocardium at steady state. Stepwise increased concentrations of nifedipine from 3 to 60 ng ml-1 in the liquid used in perfusions for 25 min. periods produced a pronounced progressive decrease in myocardial contractility to about 8%. The heart beating frequency simultaneously decreased gradually to about 76%. The mean coronary flow rate increased initially to 135% and then gradually decreased to 94%. These effects were accompanied by a decrease to about 0.27 in the ratio of the product of contraction amplitude and frequency to the oxygen consumption, a finding that was evaluated as an expression of reduced myocardial efficiency. No significant dromotropic effects were observed. |
| Databáze: | OpenAIRE |
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