Hendriks M P, Blijlevens N M A, Schattenberg A V M B, Burger D M, Donnelly J P
Department of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Bone Marrow Transplant. 2006 Oct;38(7):521-5. doi: 10.1038/sj.bmt.1705481.
Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels >or=800 microg/l.
给药后2小时测得的环孢素A(CsA)血药浓度≥800μg/L,即C2浓度,是获得最大药理效应所必需的,且与移植相关并发症如移植排斥和毒性密切相关。在一项开放交叉研究中,对21例接受异基因造血干细胞移植的患者在开始静脉输注CsA 3mg/kg/天(连续输注或每12小时输注2小时)后的第1、8和15天,在24小时内测量CsA血药水平以生成药代动力学曲线。2小时输注后的C2水平与0至4小时浓度-时间曲线下面积的相关性优于C1或C3水平(r2 = 0.62)。2小时输注CsA后,24例中有20例(83%)达到C2水平≥800μg/L,且CsA相关毒性未增加,但连续输注后23例患者中只有3例(13%)达到该水平。因此,我们建议在移植期间2小时内输注CsA,并进行C2监测以获得≥800μg/L的治疗性C2水平。