Effect of phenobarbital on metabolism and toxicity of diclofenac sodium in vitro

  Objective   To investigate the effects of phenobarbital (PB) on metabolism and toxicity of diclofenac sodium (DF-Na) in vitro.

  Methods   Rathepatocytes were isolated and cultured with sandwich method.The enzyme leakage level, cytochrome P4503A(CYP3A)activity, and metabolite content of DF-Na in cell culture medium were measured after hepatocytes or PB pre-treated hepatocytes were incubated with DF-Na in vitro.

  Results   Basic hepatic CYP3A activity grad-ually decreased with culture time.The decline of CYP3A was partially reversed by using cytochrome P450 inducer such as PB.The activities of lactic dehydrogenase(LDH), alanine transminase(ALT), and aspartate transminase(AST)and the contents of metabolite 4'-hydroxydiclofenac(4'-OH-DF)and 5-hydroxydiclofenac(5-OH-DF)in superatants were found to increase with the DF-Na exposure concentrations.But there were no significant difference between exposed group and control group.However, if the hepatocytes first were pre-treated with PB and then exposed to DF-Na, the concentrations of DF-Na metabolites and the activity of LDH in the supernatants were significantly higher than that of control group.

  Conclusion   The hepatotoxicity and metabolism of DF-Na in rathepatocytes should be increased when CYP3A activity increased.