Microsomal fraction contains the whole of hepatic UDP-glucuronyltransferase as well
as part of β-glucuronidase. The activities of the two enzymes were assayed under identical
conditions using untreated male rat liver microsomes at pH 7.5. In a 30-min incubation with
p-nitrophenol and UPD-glucuronic acid, a net glucuronide formation of 0.010 μmol-min^-1 •g• -liver^-1 was measured. In the presence of saccharolactone at concentrations selectively blocking
β-glucuronidase, the glucuronidation rate was 0.015 μmol•min^-1•g•liver^-1. Using the kinetic
parameters of β-glucuronidase (Km = 0.06 mmol/l p-nitrophenylglucuronide, V(m) = 0.075 μmol
pNP formed h^-1 •g•liver^-1) determined in the absence of UDP-glucuronic acid, to correct for the
β-glucuronidase’s interference on the glucuronidation process, a glucuronide formation of
0.011 μmol•min^-1 •g•liver^-1 was calculated.
1. Rats with biliary fistula excrete 18% of an intraperitoneal dose of [14C]imipramine (80 mg/kg) in bile within 2-5 h. Diphenylhydantoin (46 mg/kg) simultaneously administered intravenously decreases the biliary excretion of imipramine plus metabolites to 7% dose. With or without diphenylhydantoin, the highest biliary concentration of imipramine plus metabolites occurs 30-60 min after dosage. 2. With or without administration of diphenylhydantoin, 83% of the bile radioactivity is present as the conjugated 2-hydroxylated metabolites of imipramine. With imipramine alone, more conjugated 2-hydroxydesmethyl-imipramine than conjugated 2-hydroxyimipramine is excreted in the bile. Diphenylhydantoin reverses this order. 3. Administration of diphenylhydantoin does not significantly alter the concentration of imipramine plus metabolites in plasma, liver, lung and brain measured at five consecutive 30 min periods after dosage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.