Sumi Masaki, Konishi Hiroki, Ikuno Yoshihiro, Hoshino Nobuo, Minouchi Tokuzo, Yamaji Akira
Department of Hospital Pharmacy, Shiga University of Medical Science, Otsu, Japan.
Eur J Drug Metab Pharmacokinet. 2009 Jul-Sep;34(3-4):201-4. doi: 10.1007/BF03191174.
The authors report a case showing a marked change in blood tacrolimus concentration due to modification of renal function in a bone marrow transplant recipient. Blood tacrolimus concentration was well controlled after transplantation, but an approximately threefold increase in the concentration was observed on day 10 even though the dosage was unchanged. Although there were no pronounced changes in hepatic enzyme activities in serum, marked elevations of renal function test values were noted; concentrations of serum creatinine (SCr) and blood urea nitrogen (BUN) were increased by more than 300% from the original levels. The tacrolimus concentration was gradually decreased by the dose reduction, but the dose-adjusted tacrolimus blood concentration (C/D) was increased contrary to the decreased tacrolimus concentration. The C/D of tacrolimus also began to decline from several days after the recovery of Scr and BUN levels and returned to the basal level. Our finding suggests that renal function has a significant effect on the pharmacokinetic disposition of tacrolimus, although this agent is almost completely eliminated by hepatic metabolism. Careful attention should be paid to alteration in tacrolimus blood concentration, especially when renal function fluctuates during post-transplant immunosuppressive therapy.
作者报告了1例骨髓移植受者因肾功能改变导致血他克莫司浓度显著变化的病例。移植后血他克莫司浓度得到良好控制，但在第10天，尽管剂量未变，浓度却出现了约3倍的升高。虽然血清肝酶活性没有明显变化，但肾功能测试值显著升高；血清肌酐（SCr）和血尿素氮（BUN）浓度较初始水平升高超过300%。通过减少剂量，他克莫司浓度逐渐降低，但与他克莫司浓度降低相反，剂量调整后的他克莫司血药浓度（C/D）升高。SCr和BUN水平恢复数天后，他克莫司的C/D也开始下降并恢复到基础水平。我们的研究结果表明，尽管该药物几乎完全通过肝脏代谢清除，但肾功能对他克莫司的药代动力学处置有显著影响。在移植后免疫抑制治疗期间，尤其是肾功能波动时，应密切关注他克莫司血药浓度的变化。
