Murry D J, Synold T W, Pui C H, Rodman J H
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Pharmacotherapy. 1995 Mar-Apr;15(2):144-9.
To determine whether glomerular filtration rate (GFR) changes during induction chemotherapy in children with leukemia, and to examine GFR as a determinant of pharmacokinetic variability of methotrexate clearance.
Prospective, unblinded observational study in consecutive patients.
A research hospital.
Thirty-eight children newly diagnosed with acute lymphoblastic leukemia.
The patients received either high-dose methotrexate 1 g/m2 intravenously over 24 hours or low-dose methotrexate 30 mg/m2 orally every 6 hours for six doses; both regimens were followed by an intensive six-drug chemotherapy regimen given over 6 weeks. Glomerular filtration rate was determined in each subject before and at the conclusion of induction therapy.
The GFR was determined from 99mTc-DTPA serum clearance in all patients, and methotrexate clearance was estimated from serial serum concentrations in 18 of these children who received high-dose methotrexate. Median values for GFR at diagnosis (131 ml/min/1.73 m2) and after induction therapy (120 ml/min/1.73 m2) were not significantly different (p = 0.26) but were highly variable (range 49-274 ml/min/1.73 m2). Body size, age, and serum creatinine were correlated significantly with GFR at diagnosis. Amphotericin B therapy (6 patients) significantly decreased GFR (p = 0.046) without a corresponding increase in serum creatinine. Methotrexate clearance (58-155 ml/min/m2) was significantly (p = 0.007) correlated with GFR, but GFR accounted for only 37% of the variability of methotrexate clearance.
The GFR was normal but highly variable in these children with leukemia and was significantly altered by amphotericin. Our results explain little of the intersubject variability in methotrexate clearance.
确定白血病患儿诱导化疗期间肾小球滤过率（GFR）是否发生变化，并检验GFR作为甲氨蝶呤清除率药代动力学变异性的决定因素。
对连续患者进行的前瞻性、非盲观察性研究。
一家研究医院。
38名新诊断为急性淋巴细胞白血病的儿童。
患者接受24小时内静脉注射高剂量甲氨蝶呤1 g/m²或每6小时口服低剂量甲氨蝶呤30 mg/m²，共六剂；两种方案之后均采用为期6周的强化六药化疗方案。在诱导治疗前及结束时测定每名受试者的肾小球滤过率。
通过所有患者的99mTc-DTPA血清清除率测定GFR，并通过18名接受高剂量甲氨蝶呤治疗的儿童的系列血清浓度估算甲氨蝶呤清除率。诊断时（131 ml/min/1.73 m²）和诱导治疗后（120 ml/min/1.73 m²）GFR的中位数无显著差异（p = 0.26），但变化很大（范围为49 - 274 ml/min/1.73 m²）。诊断时，体型、年龄和血清肌酐与GFR显著相关。两性霉素B治疗（6例患者）使GFR显著降低（p = 0.046），而血清肌酐未相应升高。甲氨蝶呤清除率（58 - 155 ml/min/m²）与GFR显著相关（p = 0.007），但GFR仅占甲氨蝶呤清除率变异性的37%。
这些白血病患儿的GFR正常但变化很大，且受两性霉素显著影响。我们的结果几乎无法解释甲氨蝶呤清除率的个体间变异性。
