Effect of bile on cyclosporin absorption in liver transplant patients

1. We quantitated the effect of biliary diversion on cyclosporin (CyA) absorption in liver transplant patients. Multiple blood samples were obtained over one dosing interval following oral CyA administration in eight liver transplant patients before and after T-tube clamping. 2. Cyclosporin concentrations were measured by a high pressure liquid chromatographic method. 3. The mean (+/- s.d.) dose-normalized area under the blood concentration vs time curve (AUC) over a dosing interval was 5.23 (+/- 3.22) ng ml-1 h during the pre clamping period and 15.79 +/- 7.92 ng ml-1 h during the post clamping period. A significant (P less than 0.05) increase (276%) in the dose normalized AUC was observed following the T-tube clamping. 4. Analysis of bile revealed less than 1 mg (less than 1% of dose) of unchanged CyA to be eliminated in bile over 12 h. Therefore the increased CyA AUC/dose following T-tube ligation cannot be explained by enterohepatic recirculation. 5. Increased bile flow secondary to clamping of the T-tube most likely increased the absorption of CyA. Increase in CyA absorption may be due to a bile mediated increase in CyA solubility or gastrointestinal membrane permeability, or increased residence time at the site of absorption. 6. Independent of the mechanism involved, our results indicate that adjustments in CyA dosage must be made whenever external bile diversion is instituted or discontinued.