The biliary and renal excretion of
acetaminophen and its metabolites over 8 hr was determined in rats exposed to
diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with
urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under
hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of
UDP-glucuronic acid was decreased 80% in livers from
ether-anesthetized rats but was not reduced in
urethane-treated animals when compared to that in control rats. The concentration of
reduced glutathione was not affected by either
urethane or
diethyl ether. Basal bile flow was not altered by the
anesthetic agents. Bile flow rate after
acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in
hexobarbital-treated control rats, was unaltered in
urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to
diethyl ether for 1 hr. In control and
urethane-anesthetized animals, approximately 30-35% of the total
acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with
diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to
ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that
ether decreased the biliary elimination of unchanged
acetaminophen and its
glucuronide,
sulfate, and
glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged
acetaminophen and the
glutathione conjugate into bile was depressed in
urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the
glucuronide and
sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the
anesthetic agent and that
diethyl ether depresses conjugation with
sulfate and
glutathione as well as
glucuronic acid.