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Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.

Publication ,  Journal Article
Maharaj, AR; Wu, H; Zimmerman, KO; Speicher, DG; Sullivan, JE; Watt, K; Al-Uzri, A; Payne, EH; Erinjeri, J; Lin, S; Harper, B; Melloni, C ...
Published in: J Clin Pharmacol
May 2020

Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (Css ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.

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Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

May 2020

Volume

60

Issue

5

Start / End Page

636 / 647

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Maharaj, A. R., Wu, H., Zimmerman, K. O., Speicher, D. G., Sullivan, J. E., Watt, K., … Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee, . (2020). Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis. J Clin Pharmacol, 60(5), 636–647. https://doi.org/10.1002/jcph.1562
Maharaj, Anil R., Huali Wu, Kanecia O. Zimmerman, David G. Speicher, Janice E. Sullivan, Kevin Watt, Amira Al-Uzri, et al. “Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.J Clin Pharmacol 60, no. 5 (May 2020): 636–47. https://doi.org/10.1002/jcph.1562.
Maharaj AR, Wu H, Zimmerman KO, Speicher DG, Sullivan JE, Watt K, et al. Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis. J Clin Pharmacol. 2020 May;60(5):636–47.
Maharaj, Anil R., et al. “Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.J Clin Pharmacol, vol. 60, no. 5, May 2020, pp. 636–47. Pubmed, doi:10.1002/jcph.1562.
Maharaj AR, Wu H, Zimmerman KO, Speicher DG, Sullivan JE, Watt K, Al-Uzri A, Payne EH, Erinjeri J, Lin S, Harper B, Melloni C, Hornik CP, Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis. J Clin Pharmacol. 2020 May;60(5):636–647.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

May 2020

Volume

60

Issue

5

Start / End Page

636 / 647

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences