Drug metabolism in hypothermia. Uptake, metabolism and biliary excretion of pentobarbital-2-C14 by the isolated, perfused rat liver in hypothermia and euthermia.

The isolated, perfused rat liver at 37°C is able to metabolize pentobarbital-2-C°14 at rates (2.4 µmol/g/hr) comparable to those reported for the intact rat. Under conditions of hypothermia, the rate of metabolism decreases to approximately onehalf (30°C), one-third (25°C) and one-fourth (20°C) the rate at 37°C, as estimated by the disappearance of unchanged pentobarbital from the blood. The net amount of C14 retained by the liver during the four-hour perfusion is the same at all temperatures, but the quantity of C14 excreted into the bile is markedly reduced in hypothermia, due primarily to the very pronounced decrease in bile flow. Bile/blood C14 concentration ratios never exceed 3 at any time on temperature after the administration of pentobarbital-2-C14. It therefore appears that the biliary route plays a minor role in the ultimate disposition of the drug and its metabolites. The metabolites formed by the liver are excreted mainly into the blood. A comparison is made between the disposition of pentobarbital-2-C14 and another weak acid (sulfanilamide) and two weak bases (atropine and procaine) previously studied under conditions of hypothermia in the isolated rat liver.