Lymphatic transport of cyclosporin A from the abdominal cavity

Abstract

The lymphatic transport of cyclosporin A (CyA) has been studied after administration into the abdominal cavity of rats. Two abdominal administration methods were used. One was via a conventional intraperitoneal (i.p.) injection, the other by direct application on the surface of the thoracic lymph duct. To compare the lymphatic transport characteristics, intravenous (i.v.) CyA administration was also performed. The CyA dose was 5 mg/kg in all the experiments. In order to avoid contamination, thoracic lymph fluid was collected through a cannula into the left venous angle. After i.p. administration, the maximum lymphatic transport rate of CyA was determined to be 0.68 ± 0.013 (SD) μg/h, although a higher rate (1.77 ± 0.56 μg/h) was obtained after i.v. injection. By expressing the results as the percentage transferred into the thoracic lymph over a period of 24 h, the percentage amount of CyA transferred after i.p. administration was 0.10 ± 0.12% which is about 1 4 as compared to i.v. injection, 0.40 ± 0.012%. The efficiency of lymphatic absorption was dependent on the formulation in the preparation applied directly on the thoracic lymph duct. When an oily CyA solution absorbed in gauze was applied, the efficiency of lymphatic absorption (0.16 ± 0.007%) was almost the same as that observed with i.p. administration. However, when pharmaceutical additives such as polyoxyethylated castor oil derivative (nonionic surfactant, HCO-60) and saturated fatty acid (C 12, C 14, C 16 and C 18) triglyceride (Pharmasol B-115) were added to the preparation, the efficiency of lymphatic absorption recovered to the level of i.v. injection (0.37 ± 0.17%).