SULFADIMIDINE METABOLISM IN-VITRO .2. COMPARATIVE-STUDIES IN CULTUREDRAT, GOAT, SHEEP AND CATTLE HEPATOCYTES

Hydroxylation and acetylation of sulphadimidine (SDD) and the deacetyl ation of N4-acetyl SDD was investigated in cultured hepatocytes from m ale and female rats, from male and female goats and from female sheep and cattle. Significant sex differences were observed for hydroxylatio n of SDD in hepatocytes from rat and goat. In goat, sheep and cow hepa tocytes, the hydroxylation pathway is relatively important, whereas in rat hepatocytes, acetylation is predominant. Hepatocytes of air four species deacetylated N4-acetyl SDD. In ruminant hepatocytes, deacetyla ting activity was of considerable importance, whereas in rat hepatocyt es, it appeared a minor pathway of metabolism. Similar to the in vivo situation, formation of N4-acetyl SDD in cultured hepatocytes results from an equilibrium of acetylation and deacetylation. A good correlati on was found between results in isolated hepatocytes and previous find ings in vivo, both in levels of species-related activities and in acet ylation-hydroxylation ratios. In conclusion, cultured hepatocytes appe ar a useful in vitro model to study comparative sulfonamide metabolism .