Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia

Anesthesiology Research and Practice
Ryan M McAdamsDanny D Shen

Abstract

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 ...Continue Reading

References

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Citations

Oct 30, 2020·European Journal of Clinical Pharmacology·Camille E van HoornJurgen C de Graaff
Mar 3, 2021·Journal of Perinatology : Official Journal of the California Perinatal Association·Anna S CosnahanElena V Wachtel

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Methods Mentioned

BETA
sedation
cesarean section

Clinical Trials Mentioned

NCT02529202

Software Mentioned

CoolCap
NONMEM
PASS
SAAM II
NONMEM M3
R

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