Studies on absorption and metabolism of drugs in febrile animals. (III). Antipyretic effect of acetylsalicylic acid and aminopyrine and their plasma concentrations in febrile rabbits induced with lipopolysaccharide.

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Abstract
An attempt was made to clarify the mechanism of combined effect of acetylsalicylic acid (ASA) and aminopyrine (AMI) in febrile rabbits as induced by lipopolysaccharide (LPS). In addition, the possible synergic effect of both agents was studied in relation to the plasma concentration. In febrile rabbits, the plasma concentration of ASA (500 mg/kg, p.o. [orally] was a higher level than in the control, but the concentration of salicylic acid (SA), the metabolite of ASA, was similar to that in the control. The plasma concentration of AMI (100 mg/kg, p.o.) in febrile rabbits was lower than in the control. A dose-dependent antipyretic effect was seen in the successive doses from 125-500 mg/kg of ASA, and a similar tendency was also observed in AMI from 25-100 mg/kg. To observe the synergic effect of ASA and AMI, the following 3 combinations were prepared: I (ASA/AMI; 125 plus 75 mg/kg), II (ASA/AMI; 250 plus 50 mg/kg) and III (ASA/AMI; 375 plus 25 mg/kg). Plasma concentrations of ASA, SA and AMI were measured after oral administration of the preparations and these concentrations were lower than in the separate administration of ASA and AMI. The antipyretic effect of the 3 preparations was weaker than the expected value, respectively.