Konishi Hiroki, Fukushima Keizo, Saotome Takao, Hamamoto Tetsu, Eguchi Yutaka, Sudo Masatomo, Sumi Masaki, Minouchi Tokuzo, Iga Ikumi, Yamaji Akira
Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka Ohtani University, Nishikiori-kita, Tondabayashi, Japan.
Ther Apher Dial. 2010 Jun;14(3):358-63. doi: 10.1111/j.1744-9987.2009.00797.x.
Change in the pharmacokinetic disposition of an antifungal agent micafungin (MCFG) by 8-hour plasma exchange (PE) with 3200 mL replacement was examined in a stem cell transplant recipient. On pharmacokinetic analysis of the time course of the serum concentrations of MCFG, it was determined that PE shortened the elimination half-life of MCFG from 16.5 hours to 6.3 hours. Total clearance (CL(tot)) was increased from 0.366 L/h to 0.932 L/h by PE. PE-dependent clearance (CL(pe)) accounted for approximately two-thirds of CL(tot), and PE was found to contribute to the removal of nearly 40% of the total body store of MCFG. It was confirmed that a significant amount of MCFG was excluded into apheresed plasma waste. In addition, adsorption of MCFG onto plasma-separating membrane was strongly suggested, because the CL(pe) exceeded the rate of plasma apheresis and MCFG concentrations in apheresed plasma were lower than those in circulating blood collected at the same time. The marked elimination of MCFG during PE can be explained by its low volume of distribution and high affinity for serum proteins. Judging from these findings as well as those of other reports, MCFG can be considered one of the drugs most susceptible to removal by PE. Our findings suggest that an increment in the regular dose of MCFG would be required at the next administration after PE.
在一名干细胞移植受者中，研究了通过3200 mL置换量的8小时血浆置换（PE）对抗真菌药物米卡芬净（MCFG）药代动力学处置的影响。对MCFG血清浓度随时间变化过程进行药代动力学分析后确定，PE使MCFG的消除半衰期从16.5小时缩短至6.3小时。通过PE，总清除率（CL(tot)）从0.366 L/h增加到0.932 L/h。PE依赖性清除率（CL(pe)）约占CL(tot)的三分之二，并且发现PE促使清除了近40%的MCFG全身储备量。证实有大量MCFG被排至单采血浆废物中。此外，强烈提示MCFG吸附到血浆分离膜上，因为CL(pe)超过了血浆单采速率，且单采血浆中MCFG浓度低于同时采集的循环血液中的浓度。PE期间MCFG的显著清除可通过其低分布容积和对血清蛋白的高亲和力来解释。从这些发现以及其他报告的发现判断，MCFG可被认为是最易被PE清除的药物之一。我们的发现提示，在PE后的下次给药时需要增加MCFG的常规剂量。
