APPLICABILITY OF CULTURED-HEPATOCYTES DERIVED FROM GOAT, SHEEP AND CATTLE IN COMPARATIVE DRUG-METABOLISM STUDIES

1. Using trimethoprim (TMP), scoparone (SCOP), ethylmorphine (EtM), 1- naphthol (1-N) and phenol red (PhR) as test substrates, biotransformat ion activities were investigated in cultured hepatocytes from male and female rat, male and female goat, and female sheep and cattle. 2. As compared with rat hepatocytes, the total culture cytochrome P450 conte nt was relatively well maintained in ruminant hepatocytes. In 72 h, it decreased to approximately half the initial content, whereas in rat h epatocytes only 30% was maintained. In ruminant hepatocytes, sulphatio n of 1-N remained fairly stable, glucuronidation of PhR decreased grad ually, and glucuronidation of 1-N increased during the 72-h culture pe riod. 3. Oxidative metabolism of TMP was rapid in goat and sheep hepat ocytes, as compared with rat hepatocytes, reflecting species differenc es in TMP pharmacokinetics in vivo. In contrast with rat hepatocytes, 6-O-demethylation was by far the major pathway of scoparone metabolism in ruminant hepatocytes. The glucuronidation and sulphation activitie s were similar among the species. 4. In goat liver cells, sex differen ces in some oxidative biotransformations were observed, females being more active than males. In rat hepatocytes, a reverse sex difference w as observed. 5. In conclusion, cultured hepatocytes from agricultural target species appear a useful in vitro model to study comparative met abolism of veterinary drugs and other xenobiotics. Comparing rat and r uminant, sex and species differences and similarities in drug metaboli sm can be observed that reflect the in vivo situation.