Effect of atropine on gastrointestinal motility and the bioavailability of cyclosporine A in rats.

The effect of atropine on gastrointestinal motility and the bioavailability of cyclosporine A (CyA) was studied in rats. Atropine dose-dependently inhibited gastrointestinal motility, and the ID20 and ID50 doses of atropine were chosen to study the bioavailability of CyA. After oral administration of CyA, the bioavailability was about 27%, and with increasing doses of atropine the area under the concentration-time curve and the peak blood concentration of CyA decreased. Atropine had no significant effect on the time of peak blood concentration (Tmax) and the mean residence time. These data suggested that there was prehepatic metabolism of CyA; thus a luminal perfusion study was performed. When CyA was perfused through rat stomachs by a recirculation method, the content of CyA in the perfusate rapidly decreased. However, the tissue content of CyA was not very high. These results indicate that changes in gastrointestinal transit as well as gastrointestinal metabolism of CyA may be important causes of the wide variability of its absorption in humans.