PRETREATMENT WITH PARACETAMOL INHIBITS METABOLISM OF ENFLURANE IN RATS

We studied the interaction between paracetamol (acetaminophenU.S.P.) and enflurane. Sixteen rats were assigned to four groups(n=4) to receive: paracetamol 7.5 mg/100 g body weight; paracetamolplus 1% enflurane; 1% enflurane alone, or no treatment (controls).Animals were killed 6 h later. A second series of 16 were treatedidentically, but were killed after 24 h. Measurements were madeof fluoride concentrations in serum, liver and urine (indicatorsof biotransformation of enflurane), paracetamol concentrationsin urine, pathological changes in liver samples, and concentrationsof the enzymes aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in serum. Pretreatment with paracetamolsignificantly decreased urinary fluoride at 6 and 24 h afterexposure to enflurane, but decreased fluoride concentrationsin serum and liver only at 6 h after exposure to enflurane.Paracetamol concentrations in urine did not change after exposureto enflurane. Exposure to paracetamol alone increased AST andALT. At 24 h after exposure to enflurane, serum concentrationsof enzymes in rats pretreated with paracetamol were similarto those of control rats. Pretreatment with paracetamol maytherefore inhibit metabolism of enflurane. Although no hepaticdamage was observed, the increased in AST and AL T suggestedsubclinical liver damage in rats given only paracetamol.