Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
J Clin Pharmacol. 2012 Oct;52(10):1516-26. doi: 10.1177/0091270011418658. Epub 2011 Nov 8.
The aim of this study was to characterize pediatric pharmacokinetics and central nervous system exposure of naproxen after oral administration. The pharmacokinetics of naproxen was studied in 53 healthy children aged 3 months to 12 years undergoing surgery with spinal anesthesia. Children received preoperatively a single dose of 10 mg/kg oral naproxen suspension. A single cerebrospinal fluid (CSF) sample (n = 52) was collected at the induction of anesthesia, and plasma samples (n = 270) were collected before, during, and after the operation (up to 51 hours after administration). A population pharmacokinetic model was built using the NONMEM software. Naproxen concentrations in plasma were well described by a 2-compartment model. The estimated oral clearance (CL/F) was 0.62 L/h when linearly scaled by weight to 70 kg. The apparent volume of distribution at steady state (Vss/F) was 12.5 L /70 kg. The findings are consistent with previously reported pharmacokinetic parameters for children older than 5 years. Naproxen permeated into the CSF and reached CSF concentrations that were 4 times higher than unbound plasma concentrations. Based on these data, weight can be used as a basis for naproxen dosing in children older than 3 months of age.
本研究旨在描述口服萘普生后儿科人群的药代动力学特征和中枢神经系统暴露情况。在接受脊髓麻醉的 53 名 3 个月至 12 岁健康儿童中研究了萘普生的药代动力学。患儿术前给予单次 10mg/kg 口服萘普生混悬液。在麻醉诱导时采集单次脑脊液（CSF）样本（n=52），并在术前、术中及术后（给药后 51 小时）采集血浆样本（n=270）。采用 NONMEM 软件建立群体药代动力学模型。采用双室模型可较好地描述血浆中萘普生浓度。经体重线性校正至 70kg 时，估计的口服清除率（CL/F）为 0.62L/h。稳态时表观分布容积（Vss/F）为 12.5L/70kg。这些发现与以前报道的大于 5 岁儿童的药代动力学参数一致。萘普生可渗透进入 CSF，并达到高于未结合血浆浓度 4 倍的 CSF 浓度。基于这些数据，体重可作为 3 个月以上儿童萘普生给药的依据。
