Skip to main content
Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics 2/2017

01.04.2017 | Original Research Article

Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children

verfasst von: Hua-Cheng Liu, Qing-Quan Lian, Fei-Fei Wu, Cheng-Yu Wang, Wei Sun, Li-Dan Zheng, Jürgen Schüttler, Harald Ihmsen

Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009;43:2064–74.CrossRefPubMed Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009;43:2064–74.CrossRefPubMed
2.
Zurück zum Zitat Hayashi Y, Maze M. Alpha 2 adrenoceptor agonists and anaesthesia. Br J Anaesth. 1993;71:108–18.CrossRefPubMed Hayashi Y, Maze M. Alpha 2 adrenoceptor agonists and anaesthesia. Br J Anaesth. 1993;71:108–18.CrossRefPubMed
3.
Zurück zum Zitat Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007;8:115–31.CrossRefPubMed Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007;8:115–31.CrossRefPubMed
4.
Zurück zum Zitat Hannivoort LN, Eleveld DJ, Proost JH, Reyntjens KM, Absalom AR, Vereecke HE, et al. Development of an optimized pharmacokinetic model of dexmedetomidine using target-controlled infusion in healthy volunteers. Anesthesiology. 2015;123:357–67.CrossRefPubMed Hannivoort LN, Eleveld DJ, Proost JH, Reyntjens KM, Absalom AR, Vereecke HE, et al. Development of an optimized pharmacokinetic model of dexmedetomidine using target-controlled infusion in healthy volunteers. Anesthesiology. 2015;123:357–67.CrossRefPubMed
5.
Zurück zum Zitat Diaz SM, Rodarte A, Foley J, Capparelli EV. Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study. Pediatr Crit Care Med. 2007;8:419–24.CrossRefPubMed Diaz SM, Rodarte A, Foley J, Capparelli EV. Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study. Pediatr Crit Care Med. 2007;8:419–24.CrossRefPubMed
6.
Zurück zum Zitat Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, et al. A phase I, two-center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology. 2006;105:1098–110.CrossRefPubMed Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, et al. A phase I, two-center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology. 2006;105:1098–110.CrossRefPubMed
7.
Zurück zum Zitat Potts AL, Anderson BJ, Warman GR, Lerman J, Diaz SM, Vilo S. Dexmedetomidine pharmacokinetics in pediatric intensive care–a pooled analysis. Pediatr Anesth. 2009;19:1119–29.CrossRef Potts AL, Anderson BJ, Warman GR, Lerman J, Diaz SM, Vilo S. Dexmedetomidine pharmacokinetics in pediatric intensive care–a pooled analysis. Pediatr Anesth. 2009;19:1119–29.CrossRef
8.
Zurück zum Zitat Potts AL, Warman GR, Anderson BJ. Dexmedetomidine disposition in children: a population analysis. Pediatr Anesth. 2008;18:722–30.CrossRef Potts AL, Warman GR, Anderson BJ. Dexmedetomidine disposition in children: a population analysis. Pediatr Anesth. 2008;18:722–30.CrossRef
9.
Zurück zum Zitat Vilo S, Rautiainen P, Kaisti K, Aantaa R, Scheinin M, Manner T, et al. Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. Br J Anaesth. 2008;100:697–700.CrossRefPubMed Vilo S, Rautiainen P, Kaisti K, Aantaa R, Scheinin M, Manner T, et al. Pharmacokinetics of intravenous dexmedetomidine in children under 11 yr of age. Br J Anaesth. 2008;100:697–700.CrossRefPubMed
10.
Zurück zum Zitat Johnson JA. Influence of race or ethnicity on pharmacokinetics of drugs. J Pharm Sci. 1997;86:1328–33.CrossRefPubMed Johnson JA. Influence of race or ethnicity on pharmacokinetics of drugs. J Pharm Sci. 1997;86:1328–33.CrossRefPubMed
11.
Zurück zum Zitat Dutta S, Lal R, Karol MD, Cohen T, Ebert T. Influence of cardiac output on dexmedetomidine pharmacokinetics. J Pharm Sci. 2000;89:519–27.CrossRefPubMed Dutta S, Lal R, Karol MD, Cohen T, Ebert T. Influence of cardiac output on dexmedetomidine pharmacokinetics. J Pharm Sci. 2000;89:519–27.CrossRefPubMed
12.
Zurück zum Zitat Karol MD, Maze M. Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans. Baillieres Best Pract Res Clin Anaesthesiol. 2000;14:261–9.CrossRef Karol MD, Maze M. Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans. Baillieres Best Pract Res Clin Anaesthesiol. 2000;14:261–9.CrossRef
13.
Zurück zum Zitat Zhou HH, Adedoyin A, Wilkinson GR. Differences in plasma binding of drugs between Caucasians and Chinese subjects. Clin Pharmacol Ther. 1990;48:10–7.CrossRefPubMed Zhou HH, Adedoyin A, Wilkinson GR. Differences in plasma binding of drugs between Caucasians and Chinese subjects. Clin Pharmacol Ther. 1990;48:10–7.CrossRefPubMed
14.
Zurück zum Zitat American Society of Anesthesiologists. New classification of physical status. Anesthesiology. 1963;24:111. American Society of Anesthesiologists. New classification of physical status. Anesthesiology. 1963;24:111.
15.
Zurück zum Zitat Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients. Paediatr Drugs. 2008;10:49–69.CrossRefPubMed Phan H, Nahata MC. Clinical uses of dexmedetomidine in pediatric patients. Paediatr Drugs. 2008;10:49–69.CrossRefPubMed
16.
Zurück zum Zitat Lee JI, Su F, Shi H, Zuppa AF. Sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantitation of dexmedetomidine in pediatric plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852:195–201.CrossRefPubMed Lee JI, Su F, Shi H, Zuppa AF. Sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantitation of dexmedetomidine in pediatric plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852:195–201.CrossRefPubMed
17.
Zurück zum Zitat Peters AM, Snelling HL, Glass DM, Bird NJ. Estimation of lean body mass in children. Br J Anaesth. 2011;106:719–23.CrossRefPubMed Peters AM, Snelling HL, Glass DM, Bird NJ. Estimation of lean body mass in children. Br J Anaesth. 2011;106:719–23.CrossRefPubMed
18.
Zurück zum Zitat Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303–32.CrossRefPubMed Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303–32.CrossRefPubMed
19.
Zurück zum Zitat Akaike H. New look at statistical-model identification. IEEE Trans Autom Control. 1974;19:716–23.CrossRef Akaike H. New look at statistical-model identification. IEEE Trans Autom Control. 1974;19:716–23.CrossRef
20.
Zurück zum Zitat Bergstrand M, Hooker AC, Wallin JE, Karlsson MO. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011;13:143–51.CrossRefPubMedPubMedCentral Bergstrand M, Hooker AC, Wallin JE, Karlsson MO. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011;13:143–51.CrossRefPubMedPubMedCentral
21.
22.
Zurück zum Zitat Schwilden H. A general method for calculating the dosage scheme in linear pharmacokinetics. Eur J Clin Pharmacol. 1981;20:379–86.CrossRefPubMed Schwilden H. A general method for calculating the dosage scheme in linear pharmacokinetics. Eur J Clin Pharmacol. 1981;20:379–86.CrossRefPubMed
23.
Zurück zum Zitat Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76:334–41.CrossRefPubMed Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76:334–41.CrossRefPubMed
24.
Zurück zum Zitat Kohli U, Pandharipande P, Muszkat M, Sofowora GG, Friedman EA, Scheinin M, et al. CYP2A6 genetic variation and dexmedetomidine disposition. Eur J Clin Pharmacol. 2012;68:937–42.CrossRefPubMedPubMedCentral Kohli U, Pandharipande P, Muszkat M, Sofowora GG, Friedman EA, Scheinin M, et al. CYP2A6 genetic variation and dexmedetomidine disposition. Eur J Clin Pharmacol. 2012;68:937–42.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York and Basel: Marcel Dekker; 1982. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York and Basel: Marcel Dekker; 1982.
26.
Zurück zum Zitat Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part I). Clin Pharmacokinet. 1989;17:175–99.CrossRefPubMed Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part I). Clin Pharmacokinet. 1989;17:175–99.CrossRefPubMed
27.
Zurück zum Zitat Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part II). Clin Pharmacokinet. 1989;17:275–90.CrossRefPubMed Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Part II). Clin Pharmacokinet. 1989;17:275–90.CrossRefPubMed
28.
Zurück zum Zitat Kawana S, Wachi J, Nakayama M, Namiki A. Comparison of haemodynamic changes induced by sevoflurane and halothane in paediatric patients. Can J Anaesth. 1995;42:603–7.CrossRefPubMed Kawana S, Wachi J, Nakayama M, Namiki A. Comparison of haemodynamic changes induced by sevoflurane and halothane in paediatric patients. Can J Anaesth. 1995;42:603–7.CrossRefPubMed
29.
Zurück zum Zitat Roberts JK, Stockmann C, Balch A, Yu T, Ward RM, Spigarelli MG, et al. Optimal design in pediatric pharmacokinetic and pharmacodynamic clinical studies. Paediatr Anaesth. 2015;25:222–30.CrossRefPubMed Roberts JK, Stockmann C, Balch A, Yu T, Ward RM, Spigarelli MG, et al. Optimal design in pediatric pharmacokinetic and pharmacodynamic clinical studies. Paediatr Anaesth. 2015;25:222–30.CrossRefPubMed
Metadaten
Titel
Population Pharmacokinetics of Dexmedetomidine After Short Intravenous Infusion in Chinese Children
verfasst von
Hua-Cheng Liu
Qing-Quan Lian
Fei-Fei Wu
Cheng-Yu Wang
Wei Sun
Li-Dan Zheng
Jürgen Schüttler
Harald Ihmsen
Publikationsdatum
01.04.2017
Verlag
Springer International Publishing
Erschienen in
European Journal of Drug Metabolism and Pharmacokinetics / Ausgabe 2/2017
Print ISSN: 0378-7966
Elektronische ISSN: 2107-0180
DOI
https://doi.org/10.1007/s13318-016-0333-6

Weitere Artikel der Ausgabe 2/2017

European Journal of Drug Metabolism and Pharmacokinetics 2/2017 Zur Ausgabe