The biological fate of 4-butyl-4-(beta-carboxypropionyloxymethyl)-1,2-diphenyl-3,5-pyrazolidinedione (suxibuzone), antiinflammatory drug. II. The biological fate of suxibuzone (SB) after daily oral administration (author's transl)

Abstract

The biological fate of 4-butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione : suxibuzone (SB) was studied in rats and beagle dogs. Furthermore, the effects of SB on liver microsomal drug metabolizing enzyme systems in rats were compared with those of phenylbutazone (PB), after daily oral administration of SB or PB for 1 week. 1) The biological fate of SB was different in rats and dogs and in the former a sex difference was noted. 2) Liver microsomal drug metabolizing enzyme systems were induced especially in male. 3) No difference between the two drugs was noted. However, when a single oral dose of SB was administered, keeping the PB schedule the same as above, the plasma half-life of PB was markedly shortened and maximum plasma levels of metabolites were rapidly reached. These results suggest that the biological fate of SB was stimulated by the enhancement or induction of liver microsomal drug metabolizing enzyme systems due to PB and its metabolites after daily oral administration.