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Abstract
1. The metabolism of phenylbutazone has been investigated in female rats dosed with the drug by gavage.
2. The major route of excretion is via the urine; 50% of the dose being excreted in the first 24 h. A small percentage of the dose is excreted in the faeces.
3. Following administration of 14C-phenylbutazone, five labelled, unconjugated hydroxy compounds were identified in the urine by t.l.c. and autoradiography; both hydrolysable and non-hydrolysable conjugates were found. Aqueous extracts of faeces contained O conjugates of oxyphenbutazone and 4-hydroxy-oxyphenbutazone (which may be a decomposition product).
4. Urine metabolites soluble in organic solvents were quantified by inverse isotope dilution assay and spectrophotometric analysis. The major metabolite is the γ-hydroxy derivative of phenylbutazone present both as the lactone and as the straight-chain compound, while oxyphenbutazone and pγ-dihydroxyphenylbutazone are minor metabolites.