Inter-individual and inter-organ variability in the bioactivation of paracetamol by human liver and kidney tissues

Paracetamol (PAR) overdose is associated with massive hepatic injury; it may induce kidney toxicity as well. It is essential to measure organ-specific activities of related CYPs for evaluating the overdose cases. Available HPLC-based methods require high amounts of tissue samples. In order to develop liquid chromatography mass spectrometry (LC-MS)-based methods to process small amounts of human tissues, liver and kidney samples were obtained. Individual microsomes were prepared and incubated with PAR (for quantifying bioactivation), with nifedipine (for measuring CYP3A4 activity) and with p-nitrophenol (for measuring CYP2E1 activity). The small amount of tissue microsomes was sufficient to measure both the formation of NAPQI and the activities of CYP enzymes. Although the sample size in group was relatively low, both NAPQI formation and activity of CYP2E1 were significantly higher in males compared to females in kidney. Considerable variations in the metabolic capacity of individuals were observed for both organs.