Evans W E, Relling M V, de Graaf S, Rodman J H, Pieper J A, Christensen M L, Crom W R
Pharmacokinetics and Pharmacodynamics Section, St. Jude Children's Research Hospital, Memphis, TN.
J Pharm Sci. 1989 Jun;78(6):452-6. doi: 10.1002/jps.2600780605.
For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLp) for all 115 children (age 0.9-17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children less than 10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLp was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.
对于几种经肝脏代谢的药物，儿童需要更高的剂量（毫克/千克体重）才能达到与成人相当的血清浓度。吲哚菁绿（ICG）是一种常用于肝脏清除高内在清除率药物的模型底物，已在成人中得到广泛评估，但尚未在儿童中进行评估。我们评估了115名白血病儿童和9名健康成人志愿者体内ICG的处置情况。115名儿童（年龄0.9 - 17.8岁）的平均（标准差）ICG血浆清除率（CLp）显著高于成人（p = 0.0006）[14.8（7.8）对10.6（2.4）毫升/分钟/千克]。当仅将10岁以下儿童（N = 85）的清除率与成人的清除率进行比较时，差异更大[15.6（7.3）对10.6（2.4）毫升/分钟/千克；p = 0.0001]。然而，当ICG的CLp按体表面积进行标准化时，儿童的值与成人的值没有显著差异[378（204）对422（102）毫升/分钟/平方米]。这些数据为某些药物在儿童中需要更高剂量（毫克/千克）的原因提供了见解。
