Biological and Pharmaceutical Factors Affecting the Absorption and Lymphatic Delivery of Ciclosporin A from Gastrointestinal Tract

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A bsorption site and some biological and pharmaceutical factors affecting the absorption and transport of ciclosporin A (CiA) from the gastrointestinal (GI) tract into both the thoracic lymphatics and the systemic circulation have been studied in rats. In a group of rats whose gastric emptying of orally administered CiA in HCO-60 formulation, 7.0 mg/kg, was physically prevented, both the lymphatic and the systemic availabilities of CiA were negligibly low. CiA was orally administered to another group of rats whose major intestinal lymphatics as well as thoracic lymph ducts were cannulated, and it was revealed that the amount of CiA delivered to the major intestinal lymphatics was about six times greater than that of CiA transferred into the thoracic lymphatics. In bile fistulous rats, the systemic availability of CiA was predominantly decreased but the lymphatic availability was not so decreased. In contrast, solvents such as propylene glycol and polyethylene glycol affected both the systemic and the lymphatic availabilities of CiA, which were also dependent on the absorption site. In particular, the lower small intestine does not contribute to the lymphatic availability of CiA.
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