In vivo studies on toxic effects of concurrent administration of paracetamol and its [formula omitted] ester (SUR 2647 combination)

Abstract

1. 1. Single p.o. doses of paracetamol 400 and 800 mg/kg or SUR 2647 combination (free paracetamol + paracetamol-N- acetyl- dl-methionate , paracetamol/methionine ratio 2:1) equivalent to paracetamol 400 and 800 mg/kg were given to Bom:NMRI mice. Vehicle treated (1% w/v aqueous methylcellulose) mice were established as a control group. 2. 2. All treatment groups irrespective of medication caused an initial GSH depletion. However, SUR 2647 combination 400 mg/kg caused a much earlier hepatic GSH recovery than paracetamol 400 mg/kg. SUR 2647 combination 800 mg/kg caused a higher hepatic GSH level than paracetamol 800 mg/kg. 3. 3. There was no significant difference in the plasma ALAT level after SUR 2647 combination 400 or 800 mg/kg and the control group. Paracetamol 400 and 800 mg/kg caused significant plasma ALAT elevations compared to the control group. 4. 4. The addition of N- acetyl- dl-methionine esterified to paracetamol, as in the SUR 2647 combination, enhances the hepatic GSH synthesizing capacity in Bom:NMRI mice after experimental overdosage and offers protection of hepatic cell integrity as assessed by plasma ALAT level compared to paracetamol alone.