1. The anti-inflammatory agent diclofenac sodium (o-[(2,6-dichlorophenyl)amino]phenylacetic acid sodium salt) is extensively metabolized by rat, dog, baboon and man. The main metabolites were isolated from the urine of all species and from the bile of rat and dog and identified by spectroscopy. 2. Metabolism involves direct conjugation of the unchanged drug, or oxidation of the aromatic rings usually followed by conjugation. Sites of oxidation are either position 3' or 4' of the dichlorophenyl ring or, alternatively, position 5 of the phenyl ring attached to the acetic acid moiety. 3. In the urine of rat, baboon and man conjugates of the hydroxylated metabolites predominate, but the major metabolite in dog urine is the taurine conjugate of unchanged diclofenac. 4. In the bile of rat and dog, the main metabolite is the ester glucuroniade of unchanged diclofenac.

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Suntmary. The structure elucidation of C-/3-glucuronidcs of sulfinpyrazonc (AnturnnB) and phenylbutazone (Butazolidina) by spectroscopic means is reported. These conjugates represent a novel type of drug metabolites.

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Suvnvnary. The structures of the essential metabolites which are excreted by the rat after oral application of GS 13005 (O,O-dimethyl-S-[(Z-methoxy-1, 3,4-thiadiazole-5(4Hj-one-4-y1)methyl] dithiophosphate) have been elucidated. The product of final oxidation, CO,, was found to be the main metabolite (up to 36% of the dose applied). Among the degradation products excreted in the urine (up to 45% of the dose applied) the two most important were isolated. They are 4-methylsulfinylmethyl and 4-methylsulfonylmethyl derivatives respectively of the intact Z-methoxy-l,3,4-thiadiazole-5-one heterocycle (metabolites 111 and 11, in amounts of 20-25y0 and 557% of the dose applied, respectively). These metabolites originate by methylation and subsequent oxidation from the mercaptotnethyl derivative liberated after hydrolysis of the P-S bond of the dithiophosphoric acid ester.