Comparison of cyclosporin A and tacrolimus concentrations in whole blood between jejunal and ileal transplanted rats

Most immunosuppresive drugs are absorbed from the intestine after oral admi nistration, although there is some difference of bioavailability between il eum and jejunum. Using an orthotopic segmental small bowel transplantation (SBT) model in rats, we studied the pharmacokinetic profiles of cyclosporin A and tacrolimus concentrations after oral intake, comparing jejunal and i leal transplanted rats. Two types of segmental SET (jejunal and ileal SET) in a syngeneic combinati on were performed. After oral administration of cyclosporin A (10 mg kg(-1) ) or tacrolimus (5 mg kg(-1)), pharmacokinetic data were obtained from the long-surviving rats transplanted with segmental SET. To determine the effec t of additional bile on cyclosporin absorption, an emulsion of cyclosporin A with fresh bile juice was re-challenged on segmental SET rats before kill ing. A histological study was also performed by use of the intestinal graft s from the killed SET rats. A higher concentration of cyclosporin A was observed in the ileum-grafted r ats than in the rats which received the jejunal grafts. Oral bioavailabilit y of cyclosporin A in ileal SET rats tended to be increased by addition of fresh bile juice, but that in jejunal SET rats did not change. On the other hand, there was no significant difference of tacrolimus concentration betw een jejunum- and ileum-transplanted rats. Histological studies showed that the superficial mucosal layer of both grafts, but especially the ileal graf t, was markedly elongated compared with that of normal intestine. The present study showed that cyclosporin A was more actively absorbed from ileum than from jejunum in SET, but tacrolimus was absorbed equally from b oth sites. These data suggest that cyclosporin A concentration is satisfact orily controlled in the segmental ileal graft, while there is no difference of tacrolimus absorption between ileal and jejunal graft.