Morphine biliary excretion

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Cholestasis may reduce the elimination of morphine and possibly codeine, as they undergo some biliary excretion. 

Eew studies have been carried out on the biliary excretion of organic compounds in man, but Elliott ef al. (1954), while investigating the fate of C-labeled morphine in man, passed a duodenal tube in one of their subjects and took samples at intervals for 24 hours. Ey assuming that all the radio-activitj in the duodenal samples came frtim the bile and that the 24-hour bile volume was 600 ml, they were able to calculate that 7% of tlie dose was excreted in the bile, which agreed well with the amount excreted in thi feces in this time. 

Glazko and associates (1949, 1950, 1952) have studied the metabolism and excretion of the antibiotic chloramphenicol in several species. In the rat, chloramphenicol (XXVlll) (mol. wt. 323) ap >ears to be metabolized to a glucuronide (XXIX) (mol. wt. 499), which is excreted in the bile to the extent of about 30 60% of the dose in 4 hours. However, in a patient with an external bile fistula, less than 3% of the dose was excreted in the bile in a day. Thus, as with morphine, there is a species difference in the biliary excretion of chloramphenicol, the rat being a good, and man a poor, biliary excretor. 

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