Increased melibiose/rhamnose ratio in bile of rats with acute cholestasis

BACKGROUND AND AIM: Melibiose/rhamnose permeability test is used for noninvasive intestinal mucosa barrier testing. However, the possible escape route of the absorbed saccharides through either intact or impaired blood-biliary barriers has not so far been explored. The objective of the present study was therefore two-fold: First, to describe in detail the biliary pharmacokinetics of melibiose and rhamnose in rats; second, to evaluate the changes of both sugars' pharmacokinetics upon impairment of the blood-biliary barrier by acute extrahepatic cholestasis in rats. METHODS: Bile duct obstructed (BDO), sham-operated and intact (unoperated) male Wistar rats were administered, 24 h after the appropriate intervention, with a single intravenous dose of melibiose and rhamnose, and a 4-h pharmacokinetic study was performed. RESULTS: In intact animals, the biliary excretion of melibiose and rhamnose was only 0.06% and 0.4% of the administered dose, respectively, while the urinary excretion accounted for 70.6% and 61.7%, respectively. In BDO animals, the biliary excretion rate of both saccharides, especially that of melibiose, was increased with a consequent 4.4-fold rise of the biliary melibiose/rhamnose ratio, the accepted paracellular permeability indicator. Both, the renal clearance of melibiose and the urinary melibiose/rhamnose ratio remained uninfluenced by cholestasis. CONCLUSION: The present study is the first to describe in detail pharmacokinetic parameters and the biliary excretion of melibiose and rhamnose in healthy and cholestatic rats. The altered melibiose/rhamnose biliary excretion ratio in BDO rats indicates that the test is able to detect the impairment of the blood-biliary barrier in acute extrahepatic cholestasis.