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The fate of salicyluric acid (SU) after oral administration was examined in rabbits. Salicylic acid (SA) and unchanged SU were detected in the blood after oral administration of SU. However, SU only was found after intravenous administration of SU, suggesting that presystemic deconjugation of glycine was involved. After treatment of rabbits with kanamycin sulfate, complete inhibition of the formation of SA after oral administration of SU was demonstrated, indicating that the intestinal microflora was responsible for the biotransformation. Furthermore, in vitro incubation of SU with contents of gut showed that the major source of the hydrolysis was the hind gut. Based on the findings described above, the time course data for blood concentration of SU and SA after oral administration of SU have been subjected to curve-fitting by a nonlinear least squares program. The SU and SA values obtained with the simplified model containing only first-order kinetic process which is proposed by the present authors were found to agree with those obtained from experiments.

Hydrolysis of salicyluric acid in rabbit intestinal microorganisms.