Absorption of 14C bumadizone Ca and 14C phenylbutazone in isolated intestinal segments in vitro and tied off gastrointestinal sections in vivo of rats and guinea pigs

Abstract

The absorption of butylmalonic acid mono-(1,2-diphenylhydrazide) (bumadizone) and its condensation product was investigated on intestinal segments of rats and guinea pigs in vitro and in vivo. 14C-Labelled bumadizone Ca and phenylbutazone were administered. All concentrations and doses refer to the free acids of either compound. In isolated jejunal segments of rats and guinea pigs in vitro the transfer and the uptake of bumadizone by tissue is proportional to the concentration administered on the mucosal side. 320 nMol/ml bumadizone slightly decreased the absorption of water and glucose, though statistically not significantly. Phenylbutazone inhibited the absorption of water and glucose by rat jejunal segments already from concentrations of 174 nMol/ml onwards. Transfer and uptake of phenylbutazone by tissue is proportional only up to 174 nMol/ml. Beyond this concentration they decreased. In guinea pigs, transfer amounted only to 1/4 and uptake by tissue to 1/2 of those obtained from rat jejunal segments. When studying tied-off intestinal segments of rats in vivo, the jejunum was found to be the main site of abosprtion of both bumadizone and phenylbutazone. Absorption was nearly complete within 1 hr after administering a dose of 0.64 μMol. In guinea pigs it was incomplete and amounted to only 1/4 to 1/3 of that measured under the same conditions in rats. Bumadizone and phenylbutazone can be absorbed also by the stomach, the ileum and the colon. In these segments of the gastrointestinal tract, however, 1.5 to 3 times as much of this dose of phenylbutazone (0.64 μMol) was absorbed as of bumadizone. Due to its high lipid solubility phenylbutazone is transferred across the mucosal epithelium more easily than is bumadizone. However, in high doses (> 0.64 μMol) this advantage of phenylbutazone is compensated by its low water solubility. Due to higher solubility in aqueous fluids the availability for absorption of bumadizone-Ca exceeded that of phenylbutazone (1.62-97.2 μMol). Bumadizone is condensated to phenylbutazone in the organism. The liver can be regarded the main organ for this condensation reaction. In experiments on isolated jejunal segments of rats and guinea pigs in vitro, the capability of the intestinal tissue of producing phenylbutazone from bumadizone was demonstrated. Within 2 h nearly 20% of the 14C-bumadizone activity was converted into phenylbutazone in both rat and guinea pig segments after administration of bumadizone concentration of 16 μMol/ml. An increase in the bumadizone concentration is followed by a decrease in forming the condensated product.