IN-VITRO METHOD FOR ASSESSING HEPATIC DRUG-METABOLISM

We investigated an in vitro metabolic test using rat liver biopsy samp les by TLC-autoradioluminography (ARLG), with a view to developing a m ethod to rapidly assess the drug metabolizing activities of individual patients. Drug metabolizing activity was measured in liver biopsy sam ples collected from rats in four groups: a female control group, male control group, phenobarbital (PB)-administered male group and cimetidi ne (CM)-administered male group. The productivity of metabolites of 7- ethoxycoumarin (7-EC), debrisoquine (DB) and diazepam (DZ), respective ly, was lower in the female control group than in the male control gro up, but there were no differences in the productivity of metabolites o f 5-fluorouracil (5-FU) and tolbutamide (TB), respectively, between th e male and female control groups. Those of 7-EC, TB and DZ were higher in the PB-administered group than in the male control group, but thos e of DB did not differ between these two groups. Those of 5-FU, 7-EC, TB, DB and DZ were lower in the CM-administered group than in the male control group. Using TLC-ARLG, we could detect drug metabolites in ra t liver biopsy samples in a relatively short time span at low concentr ations similar to those in vivo. We could also measure drug metabolizi ng activity in cases with and without the involvement of cytochrome P4 50. When applied in clinical metabolic tests, TLC-ARLG is expected to be useful for assessing the drug metabolizing activities of patients.