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Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia
Joint Authors
McAdams, Ryan M.
Pak, Daniel
Lalovic, Bojan
Phillips, Brian
Shen, Danny D.
Source
Anesthesiology Research and Practice
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-25
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Dexmedetomidine is a promising sedative and analgesic for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH).
Pharmacokinetics and safety of dexmedetomidine were evaluated in a phase I, single-center, open-label study to inform future trial strategies.
We recruited 7 neonates ≥36 weeks’ gestational age diagnosed with moderate-to-severe HIE, who received a continuous dexmedetomidine infusion during TH and the 6 h rewarming period.
Time course of plasma dexmedetomidine concentration was characterized by serial blood sampling during and after the 64.8 ± 6.9 hours of infusion.
Noncompartmental analysis yielded descriptive pharmacokinetic estimates: plasma clearance of 0.760 ± 0.155 L/h/kg, steady-state distribution volume of 5.22 ± 2.62 L/kg, and mean residence time of 6.84 ± 3.20 h.
Naive pooled and population analyses according to a one-compartment model provided similar estimates of clearance and distribution volume.
Overall, clearance was either comparable or lower, distribution volume was larger, and mean residence time or elimination half-life was longer in cooled newborns with HIE compared to corresponding estimates previously reported for uncooled (normothermic) newborns without HIE at comparable gestational and postmenstrual ages.
As a result, plasma concentrations in cooled newborns with HIE rose more slowly in the initial hours of infusion compared to predicted concentration-time profiles based on reported pharmacokinetic parameters in normothermic newborns without HIE, while similar steady-state levels were achieved.
No acute adverse events were associated with dexmedetomidine treatment.
While dexmedetomidine appeared safe for neonates with HIE during TH at infusion doses up to 0.4 μg/kg/h, a loading dose strategy may be needed to overcome the initial lag in rise of plasma dexmedetomidine concentration.
American Psychological Association (APA)
McAdams, Ryan M.& Pak, Daniel& Lalovic, Bojan& Phillips, Brian& Shen, Danny D.. 2020. Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia. Anesthesiology Research and Practice،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1130528
Modern Language Association (MLA)
McAdams, Ryan M.…[et al.]. Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia. Anesthesiology Research and Practice No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1130528
American Medical Association (AMA)
McAdams, Ryan M.& Pak, Daniel& Lalovic, Bojan& Phillips, Brian& Shen, Danny D.. Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia. Anesthesiology Research and Practice. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1130528
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1130528