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Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
Elisabeth Norman1,2, Jenny M Kindblom3, Anders Rane4
1Department of Clinical Sciences, Pediatrics, Lund, Lund University, Lund, Sweden.
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.
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