PRETREATMENT WITH PARACETAMOL INHIBITS METABOLISM OF ENFLURANE IN RATS

We studied the interaction between paracetamol (acetaminophen U.S.P.) and enflurane. Sixteen rats were assigned to four groups (n=4) to receive: paracetamol 7.5 mg/100 g body weight; paracetamol plus 1% enflurane; 1% enflurane alone, or no treatment (controls). Animals were killed 6 h later. A second series of 16 were treated identically, but were killed after 24 h. Measurements were made of fluoride concentrations in serum, liver and urine (indicators of biotransformation of enflurane), paracetamol concentrations in urine, pathological changes in liver samples, and concentrations of the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. Pretreatment with paracetamol significantly decreased urinary fluoride at 6 and 24 h after exposure to enflurane, but decreased fluoride concentrations in serum and liver only at 6 h after exposure to enflurane. Paracetamol concentrations in urine did not change after exposure to enflurane. Exposure to paracetamol alone increased AST and ALT. At 24 h after exposure to enflurane, serum concentrations of enzymes in rats pretreated with paracetamol were similar to those of control rats. Pretreatment with paracetamol may therefore inhibit metabolism of enflurane. Although no hepatic damage was observed, the increased in AST and AL T suggested subclinical liver damage in rats given only paracetamol.