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- W2002114427 abstract "Myocardial pharmacokinetics and dynamic effects of the non-steroidal antiinflammatory drug ibuprofen were studied in isolated, spontaneously beating and retrogradely perfused rabbit hearts. Both myocardial uptake and disposition of ibuprofen showed two-compartment characteristics, which possibly reflects extracellular and intracellular binding sites. Initial and terminal kinetic half-lives were about 0.6 and 13.4 min., respectively. Vd beta was about 82 ml/g myocardial tissue. Stepwise increased ibuprofen concentrations from 30 to 160 micrograms/ml in the Krebs-Henseleit perfusion liquid produced a progressive increase in coronary flowrate up to 178%, which then decreased somewhat at higher concentrations. Preliminary observations showed a direct relaxing effect on PGF-2 alpha produced contractions in coronary vasculature. Oxygen consumption increased simultaneously to 143% at 160 micrograms/ml and then decreased. Myocardial contractility (measured by amplitude and rate of contraction) decreased progressively to about 55% at concentrations from 60-160 micrograms/ml and further to 20% at 580 micrograms/ml. Myocardial efficiency expressed as the ratio of contraction rate to oxygen consumption decreased to about 0.2. Heart beat frequency decreased simultaneously to 73%. The electrocardiographic PQ and QRS intervals increased to 143 and 139%, respectively, whereas the QT interval did not increase significantly. Asystolia occurred in some cases at ibuprofen concentrations of 580 micrograms/ml. The findings suggest that ibuprofen at therapeutic concentrations may possibly produce some coronary vasodilation accompanied by a slight negative inotropic effect. Interactions with other cardioactive drugs seem possible. The drug may cause direct cardiotoxic effects at supratherapeutic concentrations." @default.
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- W2002114427 date "2009-03-13" @default.
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- W2002114427 title "Ibuprofen, Pharmacokinetics and Pharmacodynamics in the Isolated Rabbit Heart" @default.
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- W2002114427 doi "https://doi.org/10.1111/j.1600-0773.1985.tb01261.x" @default.
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