Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio.
Br J Clin Pharmacol. 2010 Oct;70(4):557-66. doi: 10.1111/j.1365-2125.2010.03720.x.
This study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen.
The pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n= 27) or by mouth as syrup (n= 37). A single cerebrospinal fluid (CSF) sample (n= 60) was collected at the induction of anaesthesia, and plasma samples (n= 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package.
Flurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96l h(-1) 70 kg(-1) . Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (V(ss) ) was 8.1 l 70 kg(-1) . Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations.
Flurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6months, while more research is needed in neonates and in younger infants.
本研究旨在描述氟比洛芬在儿科人群中的药代动力学和中枢神经系统暴露情况。
64 名年龄在 3 个月至 13 岁的健康儿童在接受脊髓麻醉下手术时，静脉注射前给予氟比洛芬前体药物（n=27）或口服糖浆（n=37）单剂量。在麻醉诱导时采集单次脑脊液（CSF）样本（n=60），并在手术前、手术中和手术后（给药后 20 小时内）采集血浆样本（n=304）。使用 NONMEM 软件包建立群体药代动力学模型。
氟比洛芬在血浆中的浓度可以很好地用三房室模型描述。口服氟比洛芬糖浆的表观生物利用度为 81%。估计的清除率（CL）为 0.96l h(-1) 70 kg(-1) 。在包括体重作为协变量后，年龄不会影响清除率。稳态时的分布容积（V(ss) ）估计为 8.1 l 70 kg(-1) 。氟比洛芬渗透进入脑脊液，达到与未结合的血浆浓度相比高七倍的浓度。
氟比洛芬的药代动力学可以仅用体重作为 6 个月以上儿童的协变量来描述，而在新生儿和年龄较小的婴儿中需要进一步研究。
