Effects of bucolome and related barbiturate derivatives on the displacement of bilirubin from plasma albumin in vivo and in vitro.

Bucolome, one of barbiturate derivatives, lowers plasma bilirubin in Gilbert's syndrome without inductive effect on liver microsomal enzymes. To clarify the mechanism of this action, the study was performed concerning the effects of bucolome and five other closely related barbiturate derivatives including phenobarbital (PB) on plasma bilirubin in homozygous Gunn rats and on albumin-bilirubin binding in vitro. When 15 mg/100 g of bucolome was administered to Gunn rats, remarkable drop in plasma bilirubin continued for more than 48 hrs. This decrease of bilirubin was returned to preinjection level after intravenous injection of albumin. Three Gunn rats died as a result of administration of 30 mg/100 g. This dose caused no pathological change in control rats. In in vitro study, bucolome displaced bilirubin from human albumin strongly. PB had almost no effect on the plasma bilirubin in Gunn rats and the in vitro action was very small. Among the barbiturate derivatives, compounds which have cyclohexyl radicals in N position showed stronger plasma bilirubin decreasing effects in Gunn rats. From these results, a strong action to displace bilirubin from plasma albumin is concluded as the mechanism of bucolome to decrease plasma bilirubin.