Oral treatment for jaundice using immobilized bilirubin oxidase

Jaundice is characterized by an excessive accumulation of bilirubin in the blood and tissues. A novel approach to reduce plasma levels of bilirubin by blocking its enterohepatic circulation was investigated. The treatment consisted of oral administration of immobilized bilirubin oxidase, which could oxidize bilirubin in the intestine to less toxic and more water-soluble products. In vivo administration of 0.1 to 2.0 mg/day of immobilized enzyme over a four-day period to chronically jaundiced Gunn rats effectively lowered plasma bilirubin levels, but only when the molar ratio of total serum bilirubin to rat serum albumin (B/RSA) was larger than 0.35. Plasma bilirubin concentration decreased in that group from an initial value of 11.3 to 6.3 mg/dl (-40%, n = 5) after eight days. This decrease was statistically significant (p < 0.05 by Student's t test). However, administration of bilirubin oxidase to rats with a B/RSA ratio less than 0.35 (n = 10) resulted in no statistically significant change in plasma bilirubin concentration.