DRUG METABOLISM IN HYPOTHERMIA. UPTAKE, METABOLISM AND EXCRETION OF S³⁵-SULFANILAMIDE BY THE ISOLATED, PERFUSED RAT LIVER

¹ Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

This study examines the effect of hypothermia on a conjugative process of drug metabolism, namely, acetylation. S³⁵-sulfanilamide is used to follow, in the isolated, perfused rat liver, the uptake into the liver, the metabolism by the liver and the output of acetylated product into the blood and bile. Uptake of S³⁵-sulfanilamide by the liver is low, proportional to organ size and unaffected by decreased temperatures. Acetylation by the liver is depressed with temperature and exhibits a Q₁₀ of 1.6. Most of the acetylated compound appears in the blood and the rate of appearance follows an exponential curve with half-times of 70 min at 37°C to 750 min at 15°C. The total S³⁵ excreted into the bile is primarily as the free form at the early time periods. Less than 2% of the injected dose of S³⁵ appears in the bile collected from 4 hr of perfusion at 37°C, and this amount decreases with decreasing liver temperature. A comparison is made between temperature-related phenomenon for a drug, C¹⁴-atropine, which is excreted into the bile in high amounts, and for S³⁵-sulfanilamide, which is excreted into the bile in very limited quantities.

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