Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
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Aim: Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain. Methods: Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. Results: The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15–31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman′s r = −0.9, p < 0.001), volume of distribution (r = −0.8, p < 0.01) and clearance (r = −0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. Conclusion: The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin-breaking procedures.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Acta Paediatrica, International Journal of Paediatrics|
|Publication status||E-pub ahead of print - 2019 Feb 5|