Effect of s-adenosyl-l-methionine on acetaminophen pharmacokinetics in the rabbit

ABSTRACT

The effect of SAMe on acetaminophen pharmacokinetics has been studied in rabbits. SAMe administration [IM] resulted in a decrease in acetaminophen half-life from 0.85 +/- 0.12 [control group] to 0.68 +/- 0.10 h in the treated group. Acetaminophen total body clearance increased from 1.98 +/- 0.08 L/h, [control group] to 2.38 +/- 0.46 L/h in the treated group. It was not possible to determine which of the acetaminophen metabolic pathways is affected by SAMe administration because acetaminophen metabolities were not determined. To investigate the mechanism of SAMe protective effect against acetaminophen intoxication, acetaminophen was administered in the form of suspension either alone or after pretreatment with SAMe administered intramuscularly. The activity of the serum transaminase enzymes, liver glutathione level as well as histopathological examination were measured to assess liver function. SAMe administration resulted in reduction of the serum activity of alanine aminotransferase [ALT] and aspartate aminotransferase [AST] enzymes. The pathological changes in the liver produced by acetaminophen also decreased SAMe pretreatment prevented liver glutathione [GSH] depletion in acetaminophen intoxicated animals