THE CONTRIBUTION OF GUT MICROFLORA TO PARACETAMOL METABOLIsM

During the last decade, the important role of gut microflora as a special organ of the gastrointestinal system in the metabolism of drugs is well known. The aim of this study was to evaluate the role of the gut microecological population with enzymatic systems, especially beta-lyase, in the metabolism of paracetamol in mice. Two groups of 20 white male laboratory mice BALB/c, body weight 32+/-1.5 kg, were treated orally with neomycin sulphate (500 mg/kg in saline solution) and saline solution (10 ml/kg) twice daily for three days. After the treatment, the animals were given paracetamol dissolved in saline solution (200 mg/kg) intraperitoneally. The total amount of excreted paracetamol in 8 hours’ collected urine was unchanged. A difference between treated and control mice was observed regarding a highly significant reduction in the excretion of 3-methylthiometabolites. A decrease in the excretion of thiomethyl metabolites was found in the control group compared to the experimental mice. Gut microflora had a great influence on the formation of metabolic precursors, thiomethyl-conjugates, and their oxidabile products. It is obvious that the ecosystem of gut microflora has an important role in the metabolism of paracetamol resulting in a significant reduction in the excretion of 3-methylthioparacetamol by urine, the glucuronide and sulphate.