Quijano R F, Ohnishi N, Umeda K, Komada F, Iwakawa S, Okumura K
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.
Drug Metab Dispos. 1993 Jan-Feb;21(1):141-3.
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.
研究了阿托品对大鼠胃肠动力及环孢素A（CyA）生物利用度的影响。阿托品剂量依赖性地抑制胃肠动力，选择阿托品的ID20和ID50剂量来研究CyA的生物利用度。口服CyA后，生物利用度约为27%，随着阿托品剂量增加，CyA的浓度-时间曲线下面积和血药峰浓度降低。阿托品对血药峰浓度时间（Tmax）和平均驻留时间无显著影响。这些数据表明CyA存在肝前代谢；因此进行了管腔灌注研究。当通过再循环方法将CyA灌注到大鼠胃中时，灌注液中CyA的含量迅速降低。然而，CyA的组织含量不是很高。这些结果表明，胃肠转运的变化以及CyA的胃肠代谢可能是其在人体内吸收广泛变异的重要原因。
