Pharmacokinetics of Intranasally Administered Dexmedetomidine in Chinese Children

• Main Authors: Cheng-Yu Wang, Harald Ihmsen, Zhi-Yan Hu, Jia Chen, Xue-Fei Ye, Fang Chen, Yi Lu, Jürgen Schüttler, Qing-Quan Lian, Hua-Cheng Liu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-07-01
• Series: Frontiers in Pharmacology
• Subjects: dexmedetomidine; intranasal; pharmacokinetics; pediatrics; Chinese
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2019.00756/full

Background: 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.Methods: 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.Results: 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−1.Conclusions: 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.