Konjugationsreaktionen im Arzneistoffwechsel der Ratte bei akuter Äthanolbelastung

Summary

Several conjugation reactions involved in drug metabolism were studied in the rat up to 12 hours after an acute dose of ethanol (3.2 ml/kg). N-acetylation was investigated using sulfanilamide and 4-amino-antipyrine, O-glucuronidation was studied using norphenazone and 4-hydroxyphenazone.

The excretion of the conjugates of sulfanilamide and norphenazone in the urine was not affected by ethanol. However, there was an increase in the formation and excretion of the conjugates of 4-amino-antipyrine and 4-hydroxy-phenazone after ethanol. The increase in the conjugation of these two drugs is due to the inhibition of other pathways of their metabolism by ethanol. The contribution of the oxidative pathways to the metabolism of 4-amino-antipyrine decreased from the normal value of 59% to 47% after ethanol, while for 4-hydroxy-phenazone there was a decrease from 33% to 17%, under the same conditions.

By this compensatory mechanism ethanol causes a shift from an oxidative to a predominantly conjugative metabolic pattern with drugs that have such alternative pathways. These results show a highly selective type of interaction between ethanol and the pharmakokinetics of drugs. This may contribute to a better understanding of mechanisms underlying drug-ethanol-interaction.

Auszugsweise wurde bereits darüber berichtet: Schüppel, R., 1966; Schüppel, R., 1968a.