Effect of Liver Damage on Urinary Morphine Excretion

Abstract

Gross, Plant and Thompson 1 reported that liver damage by chloroform caused an increased urinary excretion of morphine in both tolerant and non-tolerant dogs. At the time of this report the presence of conjugated morphine was not recognized. Gross and Thompson 2 demonstrated that dogs excreted morphine in a combined form, and Oberst 3 in the same year showed that man also excreted a combined form of morphine. The excretion of combined morphine has shown that morphine undergoes far less destruction in the animal body than formerly supposed. While the nature of the combined morphine excretion product is still unknown, Oberst 4 believes that the morphine is conjugated with glucuronic acid. He has further demonstrated that the conjugation occurs with the hydroxyl groups and that both the phenolic and alcoholic hydroxyls may be conjugated.

Thompson and Gross 5 studying the combined morphine excretion compound in dog urine found that in this animal the combined morphine is excreted in two forms, namely a fraction which is easily hydrolyzed and the other which hydrolyzes only with more drastic procedure.

With the information that liver damage caused an increase in the excretion of free morphine in dogs, a study of the effect of liver damage on the combined morphine was undertaken in both tolerant and non-tolerant dogs.

Five non-tolerant and 3 tolerant animals were used in these experiments. The dogs were maintained on a constant diet and water intake. Morphine determinations were made before and after liver damage on a constant dose of morphine. As an indication of hepatic damage bromsulphalein dye determinations were also made before and after the liver damage. Five mg per kg of the dye were injected intravenously and the dye in 1 cc of clear serum determined at 3, 8 and 15 min after the injection. Carbon tetra