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Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children

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Abstract

Background and Objective

Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist with sedative and analgesic properties which is also used in pediatric anesthesia. Although the pharmacokinetics of dexmedetomidine have been studied in pediatric patients, there are no data for Chinese children available. As alterations in pharmacokinetics due to ethnicity cannot be ruled out, it was the aim of this study to characterize the pharmacokinetics of dexmedetomidine in Chinese pediatric patients.

Methods

Thirty-nine children aged 1–9 years undergoing surgery were enrolled in the study. Dexmedetomidine was administered as short intravenous infusion of 1–2 µg/kg in 10 min. Venous blood samples were drawn until 480 min after stopping of infusion. Dexmedetomidine plasma concentrations were measured with high-performance liquid chromatography and mass spectrometry. Pharmacokinetic modeling was performed by population analysis using linear compartment models.

Results

Data of 36 patients (age 1–9 years, weight 10–27 kg) were analyzed. The pharmacokinetics of dexmedetomidine were best described by a two-compartment model with an allometric power model and estimates standardized to 70 kg body weight. The population estimates (95 % CI) per 70 kg bodyweight were: clearance 36.2 (33.3–41.1) l/h, central volume of distribution 84.3 (70.3–91.4) l, intercompartmental clearance 82.8 (63.6–136.6) l/h, peripheral volume of distribution 114 (95–149) l, and terminal half-life 4.4 (3.6–5.3) h. Age did not show any influence on weight-adjusted parameters.

Conclusions

Chinese children showed a similar clearance, but larger volumes of distribution and longer terminal half-life when compared to studies in Caucasians.

Trial Registration

ChiCTR-OPC-14005659.

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Author notes

    Authors and Affiliations

    1. Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

      Hua-Cheng Liu, Qing-Quan Lian, Cheng-Yu Wang & Li-Dan Zheng

    2. Department of Anesthesiology, Anqing First People’s Hospital of Anhui Province, Anqing, China

      Fei-Fei Wu

    3. Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

      Jürgen Schüttler & Harald Ihmsen

    4. Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

      Wei Sun

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    1. Hua-Cheng Liu
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    Corresponding author

    Correspondence to Harald Ihmsen.

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    Funding

    This study was supported by Zhejiang provincial public welfare technology application research foundation of China (2015C33100) and Zhejiang provincial Medical and Health Science Foundation (2015KYB249).

    Conflict of interest

    Hua-Cheng Liu, Qing-Quan Lian, Fei-Fei Wu, Cheng-Yu Wang, Wei Sun, Li-Dan Zheng, Jürgen Schüttler and Harald Ihmsen declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    Informed consent

    Written informed consent was obtained from parents of all individual participants included in the study.

    Additional information

    H.-C. Liu and Q.-Q. Lian contributed equally to this work.

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    Liu, HC., Lian, QQ., Wu, FF. et al. Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children. Eur J Drug Metab Pharmacokinet 42, 201–211 (2017). https://doi.org/10.1007/s13318-016-0333-6

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