Population pharmacokinetics of pentobarbital in neonates, infants, and children after open heart surgery.
Population pharmacokinetics of pentobarbital in neonates, infants, and children after open heart surgery.
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新生儿、婴儿和儿童心脏直视手术后戊巴比妥的群体药代动力学。
DOI：
10.1016/j.jpeds.2011.04.021
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Gastonguay,MarcR
中科院分区：
文献类型：
--
作者：
Zuppa,AthenaF;Nicolson,SusanC;Barrett,JeffreyS;Gastonguay,MarcR
目的：确定戊巴比妥在新生儿、婴儿和患有先天性心脏病的幼儿心脏直视手术后的药代动力学。研究目的：35例接受戊巴比妥作为标准治疗的心脏直视手术后受试者（3.0天-4.4岁）入组。采集系列药代动力学血样。采用基于人群的非线性混合效应模型方法描述戊巴比妥的药代动力学特征，以体重为协变量，以清除率（CL）、房室间清除率、中心（V1）和外周分布容积、旁路移植术时间为协变量，以年龄和心室生理学为协变量，以CL为异速生长表示的双室模型最能描述药代动力学特征。典型婴儿（双心室生理学，6.9 kg，5.2个月，旁路移植时间60分钟）的CL为0.12 L/hr/kg，V1为0.45 L/kg，外周分布容积为0.98 L/kg。旁路移植术的效果估计不佳。对于年龄<12个月的受试者，年龄对CL的影响在考虑体重后仍然存在，并且精确估计。与双心室生理受试者相比，单心室生理受试者的清除率降低15%。
OBJECTIVESTo determine the pharmacokinetics of pentobarbital in neonates, infants, and young children with congenital heart disease after open-heart surgery.STUDY DESIGNThirty-five subjects (3.0 days-4.4 years) after open-heart surgery who received pentobarbital as standard of care were enrolled. Serial pharmacokinetic blood samples were obtained. A population-based, nonlinear mixed-effects modeling approach was used to characterize pentobarbital pharmacokinetics.RESULTSA two-compartment model with weight as a co-variate allometrically expressed on clearance (CL), inter-compartmental clearance, central (V1) and peripheral volume of distributions, bypass grafting time as a co-variate on CL and V1, and age and ventricular physiology as co-variates on CL best described the pharmacokinetics. A typical infant (two-ventricle physiology, 6.9 kg, 5.2 months, and bypass grafting time of 60 minutes) had a CL of 0.12 L/hr/kg, V1 of 0.45 L/kg, and peripheral volume of distributions of 0.98 L/kg. The bypass grafting effect was poorly estimated. For subjects <12 months age, an age effect on CL remained after accounting for weight and was precisely estimated.CONCLUSIONSPentobarbital pharmacokinetics is influenced by age and weight. Subjects with single-ventricle physiology demonstrated a 15% decrease in clearance when compared with subjects with two-ventricle physiology.