The Biological Fate of 4-Butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone), Antiinflammatory Drug. I. Plasma Levels and Urinary Excretion after Oral Administration of Suxibuzone

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Abstract
The biological fate of 4-butyl-4-(.beta.-carboxypropionyl-oxymethyl)-1,2-diphenyl-3,5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and .gamma.-hydroxyphenylbutazone (.gamma.-Hydroxy-PB) in all species, though species differences were seen in the maximum plasma levels of the respective metabolites. In dogs and monkeys, a small amount of SB was detected in the plasma during the early time of dosing. The metabolites and their maximum levels in plasma after the administration of SB were identical with those seen after the administration of PB. After administration of SB, the main metabolites found in urine were PB, Oxy-PB, .gamma.-Hydroxy-PB and their conjugates in all species, while species differences were seen in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was seen in small amount for 0-12 h. There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. Differences between male and female in maximum plasma levels of PB and .gamma.-Hydroxy-PB and in urinary excreted percent of .gamma.-Hydroxy-PB were seen only in rats. Species differences were seen in esterase activity on SB in vitro. SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB, and .gamma.-Hydroxy-PB had no effect on its action.

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