Thompson Patrick A, Murry Daryl J, Rosner Gary L, Lunagomez Simon, Blaney Susan M, Berg Stacey L, Camitta Bruce M, Dreyer ZoAnn E, Bomgaars Lisa R
Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St MC, Houston, TX 77030-2399, USA.
Cancer Chemother Pharmacol. 2007 May;59(6):847-53. doi: 10.1007/s00280-006-0388-1. Epub 2006 Nov 29.
We performed a pharmacokinetic evaluation of methotrexate (MTX) in infants with acute lymphoblastic leukemia enrolled on the Pediatric Oncology Group (POG) 9407 Infant Leukemia Study to evaluate the effects of age on MTX pharmacokinetics and pharmacodynamics.
A pharmacokinetic database of 61 patients was developed by combining MTX data obtained from 16 patients in a pharmacokinetic sub-study with data obtained for clinical care in other patients enrolled on the POG 9407 protocol. The data were analyzed for the first dose of MTX given to patients in induction/intensification therapy. Patients received MTX (4 g/m2) over 24 h at week 4 of therapy. Toxicity data were also reviewed to evaluate the incidence of common MTX toxicities during the first 6 weeks of therapy (the induction/intensification phase).
Steady-state clearance (mean+/-standard deviation) for infants aged 0-6 months was 89+/-32 ml/min/m2 compared to 111+/-40 for infants aged 7-12 months (P=0.030). In the subgroup of infants aged 0-3 months the mean steady-state clearance was 84+/-30 ml/min/m2 (P=0.026 vs. the 7-12-month group). The incidence of renal toxicity (all grades) during induction/intensification therapy was 23% in the 0-3 months age group compared to 0% (for n=27) in the group 7-12 months of age (P=0.029). There were no significant differences in hepatoxicity or mucous membrane toxicity between age groups.
A modest difference in steady-state MTX clearance is observed between younger infants (0-6 months) and older infants (7-12 months). Very young infants (0-3 months) also experienced a slightly higher incidence of renal toxicity during induction/intensification therapy. Steady-state clearance for the older infants is similar to values reported for children in other studies.
我们对参加儿童肿瘤学组（POG）9407婴儿白血病研究的急性淋巴细胞白血病婴儿进行了甲氨蝶呤（MTX）的药代动力学评估，以评估年龄对MTX药代动力学和药效学的影响。
通过将药代动力学亚研究中16例患者获得的MTX数据与POG 9407方案登记的其他患者临床护理获得的数据相结合，建立了一个61例患者的药代动力学数据库。对诱导/强化治疗中给予患者的首剂MTX数据进行分析。患者在治疗第4周接受24小时的MTX（4 g/m²）。还审查了毒性数据，以评估治疗前6周（诱导/强化期）常见MTX毒性的发生率。
0至6个月婴儿的稳态清除率（平均值±标准差）为89±32 ml/min/m²，而7至12个月婴儿为111±40（P = 0.030）。在0至3个月婴儿亚组中，平均稳态清除率为84±30 ml/min/m²（与7至12个月组相比，P = 0.026）。诱导/强化治疗期间，0至3个月年龄组的肾毒性（所有级别）发生率为23%，而7至12个月组为0%（n = 27）（P = 0.029）。各年龄组之间肝毒性或粘膜毒性无显著差异。
较年幼婴儿（0至6个月）和较大婴儿（7至12个月）之间观察到稳态MTX清除率存在适度差异。非常年幼的婴儿（0至3个月）在诱导/强化治疗期间肾毒性发生率也略高。较大婴儿的稳态清除率与其他研究中儿童报告的值相似。
