Sonneveld P, Kokenberg E, Sizoo W, Hagenbeek A, van der Steuijt K, Löwenberg B
Dr. Daniël den Hoed Cancer Center, Department of Haematology, Rotterdam, The Netherlands.
Blut. 1987 Nov;55(5):467-72. doi: 10.1007/BF00367465.
Thirteen patients in complete remission from acute nonlymphoblastic leukaemia or in chronic phase of chronic myelocytic leukaemia were treated with total body irradiation, cyclophosphamide and allogeneic bone marrow transplantation (BMT). Ciclosporin (CS) was administered for the prevention and the treatment of Graft versus Host Disease. Blood concentrations of CS were determined by Radioimmunoassay (RIA) and by High Performance Liquid Chromatography (HPLC). Trough levels of CS in peripheral blood as measured by RIA exceeded HPLC derived levels in nearly all (56/58) samples with a ratio of RIA:HPLC ranging from 2.43 +/- 1.42 at day 12 to 3.65 +/- 1.86 at day 26 after BMT (means +/- SD). A comparable ratio was found as regards the peak concentrations of CS in peripheral blood. Neither the dose of CS (0.5-3.0 mg/kg/day intravenously; 3.0-5.0 mg/kg/day per os) nor the duration of treatment (12, 19, 26 or 33 days after start of CS) were a significant factor as regards the ratio between HPLC and RIA. Concentrations of CS were also determined in bone marrow nucleated cells at 1 hour after the drug infusion had started. Here the ratio of RIA versus HPLC varied upon the duration of CS treatment with a highest ratio of 8.75 +/- 8.74 at day 12 after BMT. Bone marrow levels corresponded well with blood trough concentrations (p less than 0.01). It is concluded that the concentrations of CS in blood and bone marrow as determined by RIA and HPLC differ significantly, though consistently. At present, no advantage can be attributed to either method of analysis for routine clinical monitoring, as long as detailed information on the immunosuppressive and the toxic characteristics of CS metabolites in humans is lacking.
13例急性非淋巴细胞白血病完全缓解或慢性粒细胞白血病慢性期的患者接受了全身照射、环磷酰胺和异基因骨髓移植（BMT）治疗。给予环孢素（CS）预防和治疗移植物抗宿主病。通过放射免疫分析（RIA）和高效液相色谱法（HPLC）测定CS的血药浓度。RIA测定的外周血CS谷浓度在几乎所有（56/58）样本中均超过HPLC测定的水平，BMT后第12天RIA:HPLC比值为2.43±1.42，第26天为3.65±1.86（均值±标准差）。外周血CS峰值浓度也发现了类似的比值。CS的剂量（静脉注射0.5 - 3.0mg/kg/天；口服3.0 - 5.0mg/kg/天）和治疗持续时间（CS开始后12、19、26或33天）对于HPLC和RIA之间的比值均不是显著因素。在药物输注开始1小时后还测定了骨髓有核细胞中的CS浓度。在此，RIA与HPLC的比值随CS治疗持续时间而变化，BMT后第12天最高比值为8.75±8.74。骨髓水平与血谷浓度良好对应（p＜0.01）。结论是，通过RIA和HPLC测定的血液和骨髓中CS浓度虽始终存在显著差异，但目前在缺乏关于CS代谢产物在人体中的免疫抑制和毒性特征详细信息的情况下，常规临床监测中无法认定两种分析方法中的任何一种具有优势。
