Wang Cheng-Yu, Ihmsen Harald, Hu Zhi-Yan, Chen Jia, Ye Xue-Fei, Chen Fang, Lu Yi, Schüttler Jürgen, Lian Qing-Quan, Liu Hua-Cheng
Department of Anesthesiology, Perioperative and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
Front Pharmacol. 2019 Jul 5;10:756. doi: 10.3389/fphar.2019.00756. eCollection 2019.
Intranasal application is a comfortable, effective, nearly non-invasive, and easy route of administration in children. To date, there is, however, only one pharmacokinetic study on intranasal dexmedetomidine in pediatric populations and none in Chinese children available. Therefore, this study aimed to characterize the pharmacokinetics of intranasally administered dexmedetomidine in Chinese children. Thirteen children aged 4 to 10 years undergoing surgery received 1 µg/kg dexmedetomidine intranasally. Arterial blood samples were drawn at various time points until 180 min after dose. Dexmedetomidine plasma concentrations were measured with high performance liquid chromatography (HPLC) and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models with first-order absorption. An average peak plasma concentration of 748 ± 30 pg/ml was achieved after 49.6 ± 7.2 min. The pharmacokinetics of dexmedetomidine was best described by a two-compartment model with first-order absorption and an allometric scaling with estimates standardized to 70-kg body weight. The population estimates (SE) per 70 kg bodyweight of the apparent pharmacokinetic parameters were clearance CL/F = 0.32 (0.02) L/min, central volume of distribution V1/F = 34.2 (4.9) L, intercompartmental clearance Q2/F = 10.0 (2.2) L/min, and peripheral volume of distribution V2/F = 34.9 (2.3) L. The estimated absorption rate constant was Ka = 0.038 (0.004) min. When compared with studies in Caucasians, Chinese children showed a similar time to peak plasma concentration after intranasal administration, but the achieved plasma concentrations were about three times higher. Possible reasons are differences in age, ethnicity, and mode of administration.
鼻内给药对儿童来说是一种舒适、有效、几乎无创且简便的给药途径。然而，迄今为止，关于儿童鼻内给予右美托咪定的药代动力学研究仅有一项，且尚无针对中国儿童的相关研究。因此，本研究旨在描述中国儿童鼻内给予右美托咪定的药代动力学特征。13名年龄在4至10岁接受手术的儿童经鼻给予1μg/kg右美托咪定。在给药后直至180分钟的不同时间点采集动脉血样。采用高效液相色谱（HPLC）和质谱法测定右美托咪定血浆浓度。通过群体分析，使用具有一级吸收的线性房室模型进行药代动力学建模。给药后49.6±7.2分钟时，平均血浆峰浓度达到748±30pg/ml。右美托咪定的药代动力学最佳用具有一级吸收的二房室模型和以70kg体重标准化估计值的异速生长标度来描述。每70kg体重的群体表观药代动力学参数估计值（SE）为清除率CL/F = 0.32（0.02）L/分钟，中央分布容积V1/F = 34.2（4.9）L，房室间清除率Q2/F = 10.0（2.2）L/分钟，外周分布容积V2/F = 34.9（2.3）L。估计的吸收速率常数为Ka = 0.038（0.004）分钟。与高加索人的研究相比，中国儿童鼻内给药后达到血浆峰浓度的时间相似，但所达到的血浆浓度约高3倍。可能的原因是年龄、种族和给药方式的差异。
