Absorption of cyclosporine from rabbit small intestine in situ.

ABSTRACT

The absorption of the immunosuppressive drug, cyclosporine, from intestinal segments in the anesthetized rabbit in situ is reported. The experimental technique allows serial blood sampling with simultaneous sampling of the intestinal perfusate. The method of Loo and Riegelman for estimating the systemically absorbed fraction of the drug was used in conjunction with the in situ method. Taking the length of the rabbit small intestine as 300 cm and using the apparent permeability of cyclosporine determined in polyethylene glycol 400 (PEG 400) at a bulk fluid flow rate of 0.27 mL/min, the anatomical reserve length for cyclosporine was calculated to be -302 cm. The studies demonstrate that a significant portion of the loss of cyclosporine from rabbit small intestine cannot be accounted for as systemically absorbed drug. Furthermore, the apparent permeability coefficient of cyclosporine in these studies is so low that the length of small intestine in the rabbit is not sufficient for complete absorption of the drug from the lumen under the conditions used.