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- Title
Dosing of Continuous Fentanyl Infusions in Obese Children:A Population Pharmacokinetic Analysis.
- Authors
Maharaj, Anil R.; Huali Wu; Zimmerman, Kanecia O.; Speicher, David G.; Sullivan, Janice E.; Watt, Kevin; Al-Uzri, Amira; Payne, Elizabeth H.; Erinjeri, Jinson; Lin, Susan; Harper, Barrie; Melloni, Chiara; Hornik, Christoph P.
- Abstract
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.
- Subjects
FENTANYL; INTRAVENOUS therapy; CHILDHOOD obesity; TREATMENT effectiveness; EVALUATION
- Publication
Journal of Clinical Pharmacology, 2020, Vol 60, Issue 5, p636
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1002/jcph.1562