Choleretic mechanism and effects of cyclobutyrol in the rat: dose-response relationship

Although there is general agreement on the hydrocholeretic properties of the so-called "synthetic choleretics" on biliary secretion, related simply to the kinetics of excretion, recent studies suggest that some of these drugs also have a pharmacodynamic effect; mainly, stimulation of bile acid secretion. In the present work, we studied the biliary response to different doses of cyclobutyrol (CB) in order to determine whether this agent stimulates the secretion of bile acids and to establish the relationships between dose and the choleretic effects in anaesthetized rats. Biliary bile flow, sodium, potassium, chloride and bicarbonate outputs were found to be increased and bile acid concentrations reduced in a dose-dependent fashion after 0.40, 0.54, 0.80, 1.08 and 2.16 mmol/kg b.wt. of CB administration. All assayed doses had no effect on the bile acids secretion rate. These findings suggest that a) CB-induced choleresis is unrelated to bile acids; b) CB and bile acids do not compete for the hepatobiliar transport mechanisms, despite the anionic character of both compounds, and c) in the rat the active mechanisms involved in the biliary elimination of CB are not saturated even at the large doses employed.