Effects of diethyl ether anaesthesia on the pharmacokinetics of antipyrine and paracetamol in the rat

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Abstract
The effects of two anaesthetic procedures: continuous administration of ether throughout the periods of drug infusion and blood sampling, and brief ether administration (5 min) before drug infusion were examined. Continuous ether reduced total clearance, β, and k10 for both drugs, and in addition Vc and Vβ for antipyrine. Brief ether anaesthesia had no effect on antipyrine kinetics, but caused a decrease in total clearance, k10 and Vβ of paracetamol. The rates of distribution and redistribution of the drugs were unchanged by ether. The data suggest that ether interferes with the hepatic conjugation of paracetamol and may interfere with the hepatic oxidation of antipyrine and therefore should not be used as an anaesthetic when the kinetics of drugs with short elimination half-lives are studied. It may be used for drugs with longer half-lives.