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PLoS One. 2014 Mar 4;9(3):e90728. doi: 10.1371/journal.pone.0090728. eCollection 2014.

Evaluation of fentanyl disposition and effects in newborn piglets as an experimental model for human neonates.

Author information

1
Experimental Neonatal Physiology Unit, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Bizkaia, Spain.
2
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain.
3
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain; Drug Modeling and Consulting, Dynakin SL, Derio, Bizkaia, Spain.
4
Drug Modeling and Consulting, Dynakin SL, Derio, Bizkaia, Spain.

Abstract

BACKGROUND:

Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates.

METHODS:

Fentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn.

RESULTS:

A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment.

CONCLUSION:

The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

PMID:
24595018
PMCID:
PMC3942469
DOI:
10.1371/journal.pone.0090728
[Indexed for MEDLINE]
Free PMC Article
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