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  • Title: Pharmacokinetics and pharmacodynamics of the stable prostacyclin analogue, ZK 36 374, in the cat.
    Author: Krause W, Beckmann R, Schubert M.
    Journal: Prostaglandins Leukot Med; 1984 Aug; 15(2):187-97. PubMed ID: 6208562.
    Abstract:
    The pharmacokinetics and the pharmacologic effect on blood pressure and heart rate of ZK 36 374 were studied simultaneously in the unanaesthetized cat following intraarterial injection of 20 micrograms/kg of tritium-labelled drug. After a rapid distribution phase the plasma level of radioactive substances declined with a half-life of 44 min. The disposition of the unchanged drug was biphasic with half-lives of 7 min and 36 min. 1.5 min after injection, the systolic and diastolic blood pressures were depressed by 40 and 57% and the heart rate rose by 18%. The kinetics of the pharmacologic action was biphasic and strictly parallel to the plasma drug level. Accordingly, there was a highly significant (p less than 0.001) logarithmic correlation between the blood pressure depression and the concentration of unchanged ZK 36 374 in the plasma. ZK 36 374 was totally metabolized and excreted nearly equally with urine and feces in the form of more than eight metabolites.
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