In vitro assessment of susceptibility to toxic drug metabolites

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We made an in vitro assessment of susceptibility to drug metabolites with malotilate as substrate. Peripheral-blood mononulcear cells(PBMCs) were incubated with malotilate(0.12mM) in the presence of the NADPH-generating system and hepatic microsomes(O.025mg protein/ml). Cytotoxicity of malotilate to PBMCs was assessed by trypan blue dye exclusion and LDH release to the culture media, being found to be enhanced by the addition of the NADPH-generating system. The result indicated a significant role of the metabolites in toxicity. More interestingly, the cytotoxicity was remarkably greater in patients with malotilate-induced liver injury than in controls. This in vitro system may be useful in predicting potential toxicity of drugs for selected patients.