The effects of paracetamol on frusemide ototoxicity.

ABSTRACT

Paracetamol (acetaminophen) is currently one of the most widely used drugs. In large doses, paracetamol is both nephrotoxic and hepatotoxic, and this toxicity may arise through the production of free radicals. Recently, there has been a revival of interest in the hypothesis that aminoglycoside antibiotics are ototoxic because they facilitate free-radical production. Aminoglycosides interact strongly with loop diuretics, producing enhanced ototoxicity. The object of the present study was to determine whether paracetamol would also interact with a loop diuretic. Pigmented guinea pigs received a dose of 500 or 1000 mg/kg paracetamol via an intragastric cannula. Compound action potentials (CAP) were recorded every 10 min for 2 h. Paracetamol alone had no effect on CAP thresholds, but significantly enhanced the CAP decrement induced by frusemide given intraperitoneally 1 h after paracetamol. This enhancement was larger in animals receiving 1000 mg/kg paracetamol. Repetition of these drug doses in recovery experiments indicated that all threshold shifts recovered within 7 days.