摘要
目的探讨大剂量甲氨蝶呤（MTX）24h输注治疗儿童急性淋巴细胞白血病目标浓度个体化调整的方法。方法本研究涉及24例患儿105个疗程，检测MTX开始输注后第1和第6小时的血药浓度，根据已建立的大剂量MTX群体药物动力学模型，推算出该疗程稳态血药浓度（Css）的预测值。根据Css预测值，于MTX开始输注后第8小时调整MTX输注速度和剂量。MTX输注后第23小时再检测血药浓度（Css实测值）。结果为达目标浓度，17例（71％）患儿进行了剂量调整。45个疗程（43％）调整了剂量，42个疗程增加了剂量，3个疗程减少了剂量。早期阶段（诱导缓解和巩固治疗方案后的大剂量MTX的疗程）29个疗程中有16个疗程增加了剂量，1个疗程减少了剂量；维持阶段76个疗程中有26个疗程增加了剂量，2个疗程减少了剂量。最终有95个（90％）疗程的Css实测值达目标范围，8个疗程小于目标范围，2个疗程大于目标范围。如果不调整剂量，仅有74个（70％）疗程的Css（不调整）在目标范围。调整MTX剂量，与不调整相比，可以明显增加C鹞实测值达目标范围的疗程数（X^2=13．366，P=0．000）。在剂量不调整的60个疗程中，Css实测值和Css预测值有较好的直线相关性（r=0．487，P=0．000）；Css实测值与MTX输注后第6小时的血药浓度也有一定的直线相关性（r=0．389，P=0．002）。105个疗程MTX的总清除率（CL）实测值是（7．01±2．06）L／（m^2·h）。在所有疗程间CL相差最大达4．4倍，同一患儿不同疗程间CL相差最大达2．9倍。CL与患儿的年龄、体重和总胆红素呈直线负相关，与血磷呈直线正相关；化疗早期阶段疗程的CL有高于维持阶段疗程的倾向（P均〈0．05）。结论105个疗程大剂量MTX化疗，疗程间CL差异最大达4．4倍，需要目标浓度个体化调整。通过检测MTX输注后第1和第6小时的血药浓度，调整MTX输注速度和剂量，最终90％疗程的C鹞实测值达目标范围。早期阶段大剂量MTX化疗更需要目标浓度个体化调整。
Objective To explore the way of individualized adjustment of target range of each highdose methotrexate （MTX） 24 hours infusion to treat acute lymphoblastic leukemia in children. Methods Twenty-four children and 105 infusions were included in the study. According to 1 h and 6 h plasma MTX concentrations after infusion, based on established high-dose MTX population pharmacokinetics model, the course predicted value of drug concentration at steady state （ Css ） was calculated. MTX infusion rate and dosage was adjusted 8 h after the start according to the predicted value of Css. Then MTX concentration at 23 h （actual value of Css） was measured. Results To achieve the target range of Css, adjustments of MTX dosage were required in 17 （71%） patients. Adjustments of MTX dosage were required in 45 （43%） infusions, the dose was increased in 42 infusions and decreased in 3 infusions. There were 29 infusions of high-dose MTX during consolidation therapy （after remission induction therapy）. Among them, 16 infusions had increased dosage, and 1 infusion had decreased dosage. There were 76 infusions during maintenance therapy. Among them, 26 infusions increased dosage, and 2 infusions decreased dosage. Overall 95 （90%） infusions achieved the target range of Css, while in 8 infusions the doses were lower than the target range in 2 infusions the doses were higher than the target range. If there had been no adjustments, only 74 （70%） infusions could have achieved the target range. Adjustments of MTX dosage, compared with no adjustments, could remarkably enhance the rate of achieving the target range of Css（X^2 = 13. 366, P = 0. 000）. Among 60 infusions of no adjustments, the actual values of Css were well correlated with the predicted values of Css （r = 0. 487, P = 0. 000 ）, and the actual values of Css were also correlated with the 6 h plasma MTX concentrations after infusions （r = 0. 389, P = 0. 002）. The actual values of total clearance （CL） of MTX of 105 infusions were 7.01 ± 2.06 L/（ m^2· h）. Inter-courses variability in CL was up to 4.4-fold. Intrapatient variability in CL was up to 2. 9-fold. Predisposing factors that correlated with decreased CL of MTX were old age, heavy body weight, low blood phosphate, high blood bilirubin and infusions during maintenance therapy （P 〈 0.05 ）. Conclusions High-dose methotrexate chemotherapy needed individualized adjustment, as inter-courses variability of CL was up to 4. 4-fold among 105 infusions. According to 1 h and 6 h plasma MTX concentrations after infusion, adjusting MTX infusion rate and dosage, overall 90% infusions achieved the target range of Css. High-dose MTX infusions during consolidation therapy needed individualized adjustment of target range more.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2008年第3期203-208,共6页
Chinese Journal of Pediatrics
关键词
甲氨蝶呤
血药浓度
白血病
淋巴细胞
急性
儿童
目标浓度个体化调整
Methotrexate
Plasma concentration
Leukemia lymphocytic, acute
Child
Individualized adjustment of target range
