Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Clinical Pharmacokinetics and Pharmacodynamics of Albiglutide

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Pharmacology and optimization of thiopurines and metothrexate in inflammatory bowel disease

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  1. High-Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta-Adrenoceptor Blockade: A Randomized Clinical Trial

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Authors' Reply to Santos et al.: "Excipients in Neonatal Medicinal Products: Never Prescribed, Commonly Administered"

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Access and Use of Device-Aided Therapies for Parkinson's Disease in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

BACKGROUND: Midazolam is a first-line drug for the treatment of status epilepticus, both by buccal and intravenous administration. In children and adolescents with obesity, midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient.

OBJECTIVE: The objective of this study was to investigate the pharmacokinetics of midazolam, after intravenous administration, in obese and non-obese adolescents aged 11-18 years.

METHODS: All trial participants received a 1-µg midazolam microdose as an intravenous bolus. 13 blood samples were collected per participant at pre-specified timepoints. Plasma concentration-time data were fitted to pharmacokinetic models using non-linear mixed-effects modeling. Covariates such as weight, age, and body mass index standard deviation score were tested to explain the inter-individual variability associated with the pharmacokinetic parameters.

RESULTS: Sixty-seven adolescents were included in the analysis. The pharmacokinetics of midazolam was best described with a two-compartment model. The rate of distribution was faster, and the peripheral volume of distribution was larger in adolescents with a high body mass index standard deviation score compared with adolescents with a lower standard deviation score. Simulations revealed that long-term infusions based on total body weight could lead to high plasma concentrations in adolescents with obesity. Furthermore, simulated plasma concentrations after a fixed buccal dose indicated that adolescents with obesity may be at risk of sub-therapeutic midazolam plasma concentrations.

CONCLUSIONS: The body mass index standard deviation score was shown to have a significant influence on the peripheral volume of distribution and the inter-compartmental clearance of midazolam. The current dosing guidelines for status epilepticus, where the midazolam dose is adjusted to total body weight or age, may lead to supra- and sub-therapeutic plasma concentrations, respectively, in adolescents with obesity.

TRIAL REGISTRATION: EudraCT: 2014-004554-34.

OriginalsprogEngelsk
TidsskriftClinical Pharmacokinetics
Vol/bind59
Udgave nummer5
Sider (fra-til)643-654
Antal sider12
ISSN0312-5963
DOI
StatusUdgivet - maj 2020

ID: 58404559