Intestinal lymphatic absorption of cyclosporin A following oral administration in an olive oil solution in rats.

The intestinal lymphatic absorption of cyclosporin A (CyA) following oral administration of 6.5 +/- 0.6 and 25.2 +/- 1.4 mg kg-1 doses of the drug dissolved in an olive oil solution was studied using a thoracic duct-cannulated rat model. Cumulative lymph samples were collected for up to 114 h post-dosing and assayed by liquid scintillation counting. In this study, the estimated amount of lymphatically absorbed CyA was 0.35 +/- 0.13 and 0.47 +/- 0.29 per cent of the respective doses. In terms of the overall oral bioavailability of CyA (Fpo) by all absorptive mechanisms, the intestinal lymphatics accounted for the absorption of approximately 2 per cent of the total amount of absorbed drug. Fpo was 21.3 +/- 2.5 per cent. The results of this study suggested that lipophilicity alone was not the only factor governing intestinal lymphatic drug absorption. An explanation for the low level of lymphatic CyA absorption is presented. In addition, some reasons for the low overall oral bioavailability of CyA are discussed.