Department of Clinical Pharmacy, Children Cancer Hospital Egypt 57357, Cairo, Egypt.
Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
J Oncol Pharm Pract. 2024 Sep;30(6):983-991. doi: 10.1177/10781552231192516. Epub 2023 Aug 1.
BACKGROUND/OBJECTIVES: Cyclosporine A (CSA) dosing has been complicated by considerable intra-patient and inter-patient variability in pharmacokinetics, which is affected by different factors. We aimed to assess the various factors that might affect the CSA dose and its plasma level.
This retrospective study included paediatric cancer patients who underwent allogeneic hematopoietic stem cell transplant at the Children's Cancer Hospital Egypt 57357 from matched related donors with CSA as graft versus host disease prophylaxis. The CSA initial dose was 1.5 mg/kg IV Q12H. Then, it was titrated according to the level and drug toxicity. Cyclosporine A trough levels were assessed two to three times per week using the Emit 2000 cyclosporine-specific assay. Moreover, factors that may affect cyclosporine levels, such as age, sex, weight and the antifungal used, were analyzed to determine their effect on CSA plasma levels.
There were 119 patients included in the study. The median age was 10 years; and 43% of them used voriconazole as a prophylactic antifungal. The multivariate analysis revealed that female patients, those >9 years or on voriconazole reached the target level at low initial CSA doses. A higher probability (93%) of reaching the desired plasma level with doses 1.5 mg/kg IV Q12H was observed among patients >9 years, and on voriconazole. While those who were ≤9 years and not on voriconazole required doses >1.5 mg/kg IV Q12H, with an 89% probability of reaching the desired level.
This study suggests that the initial CSA dose should consider the patient's age and the antifungal used. Patients >9 years and/or on voriconazole may require lower initial CSA doses and could start with 1.5 mg/kg IV Q12H.
背景/目的：环孢素 A（CSA）的剂量在药代动力学方面存在很大的个体内和个体间变异性，这受到不同因素的影响。我们旨在评估可能影响 CSA 剂量及其血浆水平的各种因素。
这项回顾性研究包括在埃及儿童癌症医院 57357 从匹配的相关供体接受同种异体造血干细胞移植的儿科癌症患者，CSA 作为移植物抗宿主病预防药物。CSA 的初始剂量为 1.5mg/kg IV Q12H。然后，根据水平和药物毒性进行滴定。每周使用 Emit 2000 环孢素特异性测定法评估 2 至 3 次 CSA 谷浓度。此外，分析可能影响环孢素水平的因素，如年龄、性别、体重和使用的抗真菌药物，以确定它们对 CSA 血浆水平的影响。
研究纳入了 119 例患者。中位年龄为 10 岁；其中 43%使用伏立康唑作为预防性抗真菌药物。多变量分析显示，女性患者、年龄>9 岁或使用伏立康唑的患者，在低初始 CSA 剂量时达到目标水平。在年龄>9 岁和使用伏立康唑的患者中，观察到以 1.5mg/kg IV Q12H 剂量达到所需血浆水平的可能性更高（93%）。而年龄≤9 岁且未使用伏立康唑的患者需要剂量>1.5mg/kg IV Q12H，达到所需水平的可能性为 89%。
本研究表明，初始 CSA 剂量应考虑患者年龄和使用的抗真菌药物。年龄>9 岁和/或使用伏立康唑的患者可能需要较低的初始 CSA 剂量，可以从 1.5mg/kg IV Q12H 开始。
