Kihira K, Kadoyama M, Miyake K, Kitaura T, Kimura Y, Yoshida M, Fukuchi H
Department of Pharmaceutical Services, Hiroshima University Hospital, Japan.
Hiroshima J Med Sci. 1994 Dec;43(4):175-8.
The pharmacokinetic behavior of cyclosporine A (CyA), known as a potential immunosuppressive agent to prevent graft rejection in transplantation, was studied in patients with acute hepatitis and primary biliary cirrhosis (PBC). The ratios of blood concentration of total CyA (CyA and its metabolites), CyA, and CyA metabolites to dose/kg body weight, (t-CyA/dose, CyA/dose, and CyA-Met/dose, respectively) were significantly higher in patients with hepatitis than those in renal transplantation. In PBC patients these ratios showed a tendency to be smaller than those in renal transplantation, but were not significant. The ratio of CyA-Met/CyA was higher in the patients with hepatitis and PBC than that in renal transplantation. It was highest in the patients with PBC. The ratio of CyA-Met/CyA was significantly increased with a decrease of liver functions evaluated by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil). These results indicate that hepatic function affects the pharmacokinetic behavior of CyA and the increased ratio of CyA-Met/dose could be caused by a possible increased efflux of metabolites into the blood circulation due to impaired bile excretion. These results also indicate the importance of therapeutic drug monitoring (TDM) in the use of CyA with patients with hepatic dysfunction.
环孢素A（CyA）作为一种潜在的免疫抑制剂，用于预防移植中的移植物排斥反应，其药代动力学行为在急性肝炎和原发性胆汁性肝硬化（PBC）患者中进行了研究。肝炎患者中总CyA（CyA及其代谢产物）、CyA和CyA代谢产物的血药浓度与剂量/体重的比值（分别为t-CyA/剂量、CyA/剂量和CyA-Met/剂量）显著高于肾移植患者。在PBC患者中，这些比值显示出比肾移植患者小的趋势，但不显著。肝炎和PBC患者中CyA-Met/CyA的比值高于肾移植患者。在PBC患者中该比值最高。CyA-Met/CyA的比值随着血清谷草转氨酶（GOT）、谷丙转氨酶（GPT）和总血清胆红素（t-Bil）评估的肝功能下降而显著增加。这些结果表明肝功能影响CyA的药代动力学行为，CyA-Met/剂量比值的增加可能是由于胆汁排泄受损导致代谢产物向血液循环中流出可能增加所致。这些结果还表明在肝功能不全患者使用CyA时治疗药物监测（TDM）的重要性。
