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O-8 The pharmacokinetics of fentanyl and its derivatives in children – a comprehensive review
  1. Ziesenitz1,
  2. Vaughns2,
  3. Atkinson3,
  4. Koch4,
  5. Mikus5,
  6. Van den Anker4
  1. 1University Children’s Hospital Basel, BASEL, Switzerland
  2. 2Division of Anaesthesia and Pain Medicine, Children’s National Health System, WASHINGTON, DC, USA
  3. 3University of Bern and University of Basel Children’s Hospital, BASEL, Switzerland
  4. 4Division of Paediatric Pharmacology, University of Basel Children’s Hospital, BASEL, Switzerland
  5. 5Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital, HEIDELBERG, Germany

Abstract

Background Fentanyl and its newer derivatives sufen-tanil, alfentanil and remifentanil are strong opioid anal-gesics frequently used in pediatricpatients. Despite this extensive use insufficient information on the PK of these drugs in neonates, infants, children and adolescents is available. The goal of this analysis was to perform a thor-ough review of the PK properties of fentanyl and its deriv-atives in children of all age groups.

Methods PubMed was searched using specific terms re-lated to the pharmacology of fentanyl and its derivatives in the paediatric population. Original articles and reviews regarding the PK, PD, efficacy and safety were included. A meta-analysis of PK data was conducted using a ran-dom effects model. Individual PK data was re-analysed for subgroups.

Results Of the retrieved 372 articles, clinical studies were the most frequent, followed by case series, case and short reports, and reviews. Fentanyl and its derivatives show a satisfactory safety profile in children. Forty four eligible PK studies contained data from 821 paediatric patients, including more than 46 preterm infants, 64 neonates, 115 infants and toddlers, 188 children, and 28 adolescents. Special populations comprised preterm infants, children with chronic renal or liver disease, undergoing extracor-poreal circulation, or with obesity. Pooled mean fentanyl clearance (CL) was 14.56 (95% CI 12.16, 16.74) mL/min/kg and volume of distribution (Vd) was 5.46 (2.64, 10.27) L/kg. Mean sufentanil CL was 19.43 (12.77, 26.09) mL/min/kg and Vd was 2.39 (1.63, 3.15) L/kg. Alfentanil CL was 6.23 (4.44, 8.02) mL/min/kg and Vd was 0.57 (0.42, 0.72) L/kg. There was only weak correlation between body weight (BW) and both CL and Vd of fentanyl (r2=0.22 and r2=0.43, p=0.0054 and p<0.0001) in preterm infants, neonates and young infants. Sufentanil CL correlated strongly with BW (r2=0.67, p<0.0001) and age (r2=0.62, p<0.0001). Alfen-tanil CL exhibited strong correlation with both age and BW (r2=0.71 and 0.72, both p<0.0001). There was an iden-tical correlation with both age and BW for Sufentanil Vd (both r2=0.81, p<0.0001) and Alfentanil Vd (both r2=0.59, both p<0.0001). While remifentanil CL correlated equally strong with age and BW (r2=0.73 vs. 0.69, both p<0.0001), BW had a greater impact on the Vd than age (r2=0.73, vs. 0.63, both p<0.0001).

Conclusion There are profound differences between the fentanyl derivatives and their PK correlations with BW. Fu-ture studies should be designed to assess the PK and PD of fentanyl and its derivatives in all paediatric subpopulations.

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