Ueda C T, Lemaire M, Gsell G, Misslin P, Nussbaumer K
Biopharm Drug Dispos. 1984 Apr-Jun;5(2):141-51. doi: 10.1002/bdd.2510050207.
The oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg-1 doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose-dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration-time curves suggested that the rate of CyA absorption for all four doses was an apparent zero-order process. Moreover, the rate of CyA absorption appeared to be dose-dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose-dependent characteristics in this study. F increased from 0.13 after the 6 mg kg-1 dose to 0.22 with the 18 and 23 mg kg-1 doses (p less than 0.05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first-order rate constant (beta) and corresponding elimination half-life (T 1/2 beta) of approximately 4-5 h, 0.030 h-1 and 21-28 h, respectively, were similar for all CyA doses. Moreover, no difference in beta was observed after oral or intravenous drug administration. Absorption lag times of 1-2 h were found. The results suggested that the dose-dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/or metabolized by the gastric mucosa.
以橄榄油溶液给大鼠分别灌胃6、12、18和23mg/kg剂量的环孢素A（CyA），研究其口服吸收情况，以确定胃肠道对CyA的吸收是否存在剂量依赖性。利用在各剂量给药后不同时间采集的系列血样，对所得血药浓度-时间曲线进行分析，结果表明，所有四个剂量的CyA吸收速率均为表观零级过程。此外，CyA的吸收速率似乎存在剂量依赖性，随CyA剂量增加而升高。同样，在本研究中，CyA的吸收程度（F）也呈现出剂量依赖性特征。F值从6mg/kg剂量后的0.13增加至18和23mg/kg剂量后的0.22（p<0.05）。在本研究中，所有CyA剂量的药物吸收持续时间（T）、末端一级速率常数（β）和相应的消除半衰期（T 1/2β）观测值分别约为4-5小时、0.030 h-1和21-28小时，且均相似。此外，口服或静脉给药后β值无差异。发现吸收滞后时间为1-2小时。结果表明，本研究中观察到的CyA剂量依赖性吸收可能与橄榄油对胃排空的影响有关，且CyA可能在胃液中不稳定和/或被胃黏膜代谢。
