TY - JOUR T1 - III. STUDIES ON QUINIDIN JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 335 LP - 345 VL - 30 IS - 4 AU - SOMA WEISS AU - ROBERT A. HATCHER Y1 - 1927/02/01 UR - http://jpet.aspetjournals.org/content/30/4/335.abstract N2 - 1. Quinidin present in tissues may be recovered almost quantitatively by liquefying the tissues with hot solution of sodium hydrate and shaking the solution with chloroform. It can be extracted from one million parts of blood by shaking the latter with 25 volumes of chloroform. It can be estimated quantitatively in extracts of tissues by titration with bromin water. 2. About 95 per cent of an intravenous dose of quinidin leaves the blood within five minutes; the concentration in the blood then sinks gradually and about one per cent of that injected intravenously is present in the circulation after an interval of an hour. After an interval of from three to four hours only traces remain in the blood. The rate of disappearance from the blood varies in different individuals. 3. The capillaries of the organs fix quinidin loosely at first and much of that so fixed can be removed by perfusion. Probably all capillaries of the body fix it to some degree. 4. The concentration of quinidin in the various organs changes constantly. The lungs fix it in the greatest concentration at first because it reaches them in the highest concentration; later the kidneys and liver hold it in higher concentration than the lungs. 5. The toxicity of quinidin varies widely with the rate of its intravenous injection. The average fatal dose of the sulphate for the cat when it is injected at the rate of 5 mgm. per kilogram per minute is about 80 mgm. per kilogram. Much smaller doses are sometimes fatal with rapid injection. 6. The essential elimination is practically complete within from three to four hours, after which the animal requires as much to cause death as one that had not received a previous dose. The organs, including the liver and kidneys, still retain the poison in concentrations about equal to that which they would hold were the alkaloid distributed uniformly throughout the body and had none been eliminated but the concentration in these organs is somewhat lower than it is shortly after the rapid intravenous injection of a nearly fatal dose. 7. The liver destroys quinidin during perfusion at approximately the same rate that it destroys quinin. 8. The behavior of quinidin in the body resembles that of quinin in the various ways in which its behavior has been determined by us. 9. Toxic doses of quinidin or quinin are not synergistic with the toxic action of ouabain (a digitalis body) on the heart. ER -