PMID: 7336949Apr 1, 1981Paper

Myocardial pharmacokinetics and pharmacodynamics of nifedipine in the isolated rabbit heart

Acta Pharmacologica Et Toxicologica
G Nielsen-Kudsk, J Askholt

Abstract

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 ...Continue Reading

References

Jan 1, 1977·Annual Review of Pharmacology and Toxicology·A Fleckenstein
Feb 15, 1979·European Journal of Pharmacology·S Thorens, G Haeusler
Oct 22, 1979·The American Journal of Cardiology·F A Heupler, W L Proudfit
Oct 22, 1979·The American Journal of Cardiology·S GoldbergJ A Kastor
Dec 18, 1978·European Journal of Clinical Pharmacology·O L Pedersen, E Mikkelsen
Nov 1, 1977·Clinical Pharmacology and Therapeutics·M GuazziP Moruzzi
Apr 1, 1976·Acta Pharmacologica Et Toxicologica·H RefsumK Landmark
Mar 1, 1980·Acta Pharmacologica Et Toxicologica·F Nielsen-Kudsk, S Quist
Apr 1, 1980·Acta Pharmacologica Et Toxicologica·F Nielsen-Kudsk, S Quist
Mar 1, 1980·Canadian Journal of Physiology and Pharmacology·J Church, T T Zsotér
Sep 1, 1980·Acta Pharmacologica Et Toxicologica·F Nielsen-Kudsk, J Askholt

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Citations

Jan 1, 1983·European Journal of Clinical Pharmacology·K E PedersenF Nielsen-Kudsk
Feb 1, 1985·Acta Pharmacologica Et Toxicologica·J Askholt, F Nielsen-Kudsk
Jul 1, 1986·Acta Pharmacologica Et Toxicologica·J Askholt, F Nielsen-Kudsk
Jul 1, 1983·The Journal of Surgical Research·S Okamatsu, A M Lefer

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