Drug metabolism in hypothermia. Uptake, metabolism and excretion of C14-procaine by the isolated, perfused rat liver.

This study examines the effect of hypothermia on the process of hydrolysis with procaine, labeled with C 14 in the carboxyl position, as the prototype drug. In the isolated, perfused rat liver preparation, the C 14 tag was used to follow liver uptake, metabolism and biliary excretion of the drug. Results show that the initial rate of C 14 uptake by the liver decreases with decreasing temperature. Under euthermic conditions the rate of procaine hydrolysis approximates its rate of liver uptake, but in hypothermia hydrolysis is slower than uptake. Further metabolism of the hydrolysis products is indicated by the appearance of at least four metabolites, in addition to procaine, in the bile. The C 14 label from the administered C 14 -procaine shows concentration ratios for bile/blood of about 30. Further details of the various steps in its movement from blood into bile are considered. The excretion of C 14 into the bile is temperature-dependent; maximum concentrations are reached more slowly, concentrations are lower, and the percentage of the injected dose excreted in 4 hr is less under hypothermic conditions.