摘要
目的考察大剂量甲氨喋呤(HDMTX)在儿童急性淋巴细胞性白血病(ALL)的群体药动学(PPK)特征。方法18例患儿随机接受3种HDMTX方案共43例次,1g·m-2静滴36h,3和5g·m-2静滴24h分别为14,16和13例次。用荧光偏振免疫法(FPIA)测定MTX血浆浓度,用NONMEM软件进行模型拟合和群体药动学参数的计算。结果PPK模型为:中央室的清除率(CL1)=6.50×100.0160×(Age-10)(L·h-1·m-2),室间清除率(CL2)=0.169(L·h-1·m-2),中央室的表观分布容积(V1)=16.2×100.00236×(Age-10)(L·m-2),周边室的表观分布容积(V2)=1.96×100.0130×(145-Height)+0.087×(Age-10)(L·m-2)。CL1,CL2,V1,V2的群体标准值(个体间RSD)分别为6.50L·h-1·m-2(16.2%),0.169L·h-1·m-2(极小),16.2L·m-2(极小),1.96L·m-2(21.1%)。大多数患者的拟合值与观测值接近,拟合较好。结论患者的年龄、身高对PPK参数有影响,本试验估算的参数误差在相对较小的范围内,模型拟合情况较好,可以为临床制定个体化用药方案服务。
Abstract
OBJECTIVE To evaluate the change of methotrexate (MTX) concentration in plasma,and to discribe the population pharma-cokinetic(PPK) characteristics for individualyzing methotrexate dosage regimen. METHODS Total 43 courses of HDMTX were administered to 18 patients. The numbers of patients who were given 1 g·m-2 MTX over 36 h, 3 and 5 g·2m-2 MTX over 24 h were 14, 16 and 13, respectively. Fluorescence polarization immunoassay (FPIA) was used to determine MTX concentrations. Population pharmacokinetic model and parameters were estimated by NONMEM software. MTX concentrations during and after MTX infusion were simulated.RESULTS The following population parameters were obtained using a two-compartment model: CL1(clearance of central compartment, L·h-1·2m-2)=6.50× 100.0160×(Age-10)(inter-individual variability,16.2%) , CL2(inter-compartmental clearance,L·h-1·m-2)=0.169 (extremely small),V1(central volume, L·m-2) = 16.2 ×100.00236×(Age-10)(extremely small), V2 (peripheral volume, L·m-2) =1.96× 100.013×(145-Height)+0.0827×(Age-10)(21.1%).The typical values(inter-individual variability) of CL1,CL2, V1, V2 were 6.5 L·h-1·m-2 (16.2%),0.169 L·h-1·m-2(extremely small),16.2 L·m-2(extremely small),1.96 L·m-2(21.1%).For most patients,the predicted values were close to the observed values.CONCLUSION The age of patients has significant influence on the clearance and central volume. A good fitness is derived from the PPK that should provide service for clinical appropriate MTX dosage regimen.
关键词
急性淋巴细胞性白血病 /
甲氨喋呤 /
荧光偏振免疫法 /
群体药动学
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Key words
acute lymphoblastic leukemia /
methotrexate /
fluorescence polarization immunoassay /
population pharmacokinetics
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杨丽华;卢新天;卢炜;吴克华;华瑛;赵卫红.
大剂量甲氨喋呤在急性白血病患儿体内的群体药动学[J]. 中国药学杂志, 2005, 39(13): 1007-1011
YNG Li-hu;LU Xin-tin;LU Wei;WU Ke-hu;HU Ying;ZHO Wei-hong.
Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukemia [J]. Chinese Pharmaceutical Journal, 2005, 39(13): 1007-1011
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脚注
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