Localization of Cyclosporin a Absorption in Rat Small Bowel and the Effect of Bile

Cyclosporin A absorption was examined after the instillation of approximately 2 mg/kg into four segments (mean length 15 cm) of rat small bowel, isolated in situ in fed Wistar female rats: SI (duodenum and proximal jejunum distal to the common bile duct); SII (distal jejunum); SIII (proximal ileum) and SIV (distal ileum). 2. Cyclosporin A concentrations in whole blood were assayed by an enzyme-mediated immunoassay for up to 4 h in samples drawn from the femoral vein and used to determine the following pharmacokinetic parameters: the area under the blood cyclosporin A concentration versus time curve (AUC, 0-4 h), the maximum blood concentration of cyclosporin A (Cmax.), the time to reach Cmax. (tmax.), the absorption half-life (t1/2a), the elimination half-life (t1/2 lambda), and the mean residence time (MRT). 3. Cyclosporin A absorption in SI (AUC, 991 micrograms l-1 h) was nearly double that in more distal segments and decreased progressively (SII, 533 micrograms l-1 h; SIII, 470 micrograms l-1 h; SIV, 419 micrograms l-1 h). There were corresponding differences in Cmax.: 327 micrograms/l in SI and 201 micrograms/l, 169 micrograms/l and 151 micrograms/l in SII, SIII and SIV, respectively. Tmax. was shorter in SIV (0.9 h) than in other segments (1.3-1.5 h), but there were no significant differences between the segments for t1/2a, t1/2 lambda or MRT. 4. In the presence of continuous bile flow (diverted via a cannula for SIV), cyclosporin A absorption significantly increased by 23% in SI and by 50% in SIV, but the differential between absorption in SI and SIV was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)