Awni W M, Kasiske B L, Heim-Duthoy K, Rao K V
College of Pharmacy, University of Minnesota, Minneapolis.
Clin Pharmacol Ther. 1989 Jan;45(1):41-8. doi: 10.1038/clpt.1989.7.
Sequential changes in the pharmacokinetics of cyclosporine (CsA) and metabolites M1, M17, and M21 were determined, 1, 3, and 12 weeks after initiation of CsA therapy in 21 renal transplant recipients. Concentrations of CsA and its metabolites were measured by HPLC. The dose-adjusted AUC (AUCSS tau) and 24-hour trough (C24trough) level of CsA and the metabolites increased significantly during the study period. However, there was no change in the AUCSS tau ratio of each of the metabolites to that of CsA, suggesting that CsA metabolism did not change. However, the factors that alter the binding and distribution of CsA (i.e., hematocrit, plasma proteins, and lipoproteins) showed a significant rise during the study period, and the rise correlated well with the observed changes in AUCSS tau and C24trough. Thus alterations in the distribution and binding of CsA and its metabolites in blood, rather than reduction in the metabolism of CsA, may explain changes in CsA pharmacokinetics over time.
在21名肾移植受者中，于环孢素（CsA）治疗开始后的第1、3和12周，测定了CsA及其代谢产物M1、M17和M21药代动力学的序贯变化。通过高效液相色谱法测量CsA及其代谢产物的浓度。在研究期间，CsA及其代谢产物的剂量调整AUC（AUCSS tau）和24小时谷浓度（C24trough）显著增加。然而，各代谢产物与CsA的AUCSS tau比值未发生变化，提示CsA代谢未改变。然而，在研究期间，改变CsA结合和分布的因素（即血细胞比容、血浆蛋白和脂蛋白）显著升高，且该升高与观察到的AUCSS tau和C24trough变化密切相关。因此，CsA及其代谢产物在血液中的分布和结合改变，而非CsA代谢减少，可能解释了CsA药代动力学随时间的变化。
