Pharmacokinetic and Pharmacodynamic Modeling of Clonidine and Midazolam for Sedation in Pediatric Intensive Care
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10504117" target="_blank" >RIV/00064165:_____/25:10504117 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10504117
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kxYJfYCtV4" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kxYJfYCtV4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/pan.70050" target="_blank" >10.1111/pan.70050</a>
Alternative languages
Result language
angličtina
Original language name
Pharmacokinetic and Pharmacodynamic Modeling of Clonidine and Midazolam for Sedation in Pediatric Intensive Care
Original language description
Background: Clonidine and midazolam are routinely used in the pediatric intensive care unit for pain and sedation management, but target concentration and optimal dose are poorly defined for both drugs. The CloSed study is a multicenter, double-blind, randomized, active-controlled noninferiority trial with a 1:1 randomization between clonidine and midazolam. Aims: Data from the prematurely terminated CloSed trial were used to study the population pharmacokinetic-pharmacodynamic relationships for clonidine and midazolam to inform the optimal use of both drugs in mechanically ventilated children. Methods: Twenty-eight patients (0-6 years) were included; 13 received midazolam, and 15 received clonidine. Morphine was administered to all patients as background analgesia. A total of 317 and 306 observed COMFORT-B scores for midazolam and clonidine, respectively, were available to build the pharmacokinetic-pharmacodynamic model. Pharmacokinetic models were developed using findings from previously published pharmacokinetic studies to augment the trial data. A one-compartment model described clonidine pharmacokinetics, while a single compartment for midazolam and its metabolite described its pharmacokinetics. A joint inhibitory sigmoid model that included a postanesthesia effect was used to describe the concentration-effect relationship, using the COMFORT-B score as the pharmacodynamic endpoint. Results: The final models adequately described the observed data. Simulations based on the final models showed that a clonidine dose of 4 μg/kg loading dose followed by a 3 μg/kg/h infusion, and a midazolam dose of 200 μg/kg loading dose followed by a 200 μg/kg/h infusion would be required to achieve adequate sedation. Conclusion: The CloSed data suggest that higher doses of clonidine and midazolam than are commonly used in clinical practice should be considered to provide adequate sedation in critically ill children.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30209 - Paediatrics
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Paediatric Anaesthesia
ISSN
1155-5645
e-ISSN
1460-9592
Volume of the periodical
35
Issue of the periodical within the volume
12
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
1053-1062
UT code for WoS article
001586371100001
EID of the result in the Scopus database
2-s2.0-105021324530