Bile salt-independent flow

The bile salt-independent pathway depends on osmotically active solutes such as glutathione and bicarbonate to generate water flow into the canaliculi. It has been shown that bile flow continues at zero bile salt excretion, i.e. a bile salt-independent process. 

Until recently, it was considered that hepatic bile flow was still possible even if no bile acids were excreted. This portion of bile flow was termed bile acid independent and was estimated to account for around one-third of canalicular bile flow in man (B33, P15). More recent evidence suggests that the relationship between bile flow and bile acid excretion is curvilinear, so that bile flow decreases progressively more rapidly as bile acid excretion rates decrease to very low values (B2, B24). Bile-salt-independent bile flow may therefore be much lower than previously thought and represent only a very small fraction of total bile flow (B24). 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

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