Orlistat treatment increases fecal bilirubin excretion and decreases plasma bilirubin concentrations in hyperbilirubinemic Gunn rats.

Objective: To determine whether serum levels of unconjugated bilirubin (UCB) can be decreased by enhancing fecal fat excretion.

Methods: Gunn rats were fed a high-fat diet (control) or the same diet mixed with the lipase inhibitor orlistat. At regular intervals, plasma UCB concentrations were determined and 72-hour fat balances were performed.

Results: Orlistat treatment decreased plasma UCB concentrations (at 3 weeks; 100 mg/kg, -33%+/-8%, P<.05; 200 mg/kg, -46%+/-10%, P<.01). Within days of treatment, orlistat treatment increased fecal excretion of UCB (at day 3; +220%, P<.05). During 24 weeks of orlistat treatment (200 mg/kg diet), the plasma bilirubin concentrations were continuously approximately 35% lower than in control rats. Plasma UCB concentrations were inversely correlated with the amount of fecal fat excretion (n=12, r=-0.87, P<.001).

Conclusions: In Gunn rats, orlistat treatment increases the fecal excretion of fat and enhances the disposal of UCB. This approach could lead to novel strategies for prevention and treatment of unconjugated hyperbilirubinemia in patients.