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

Differences in fentanyl pharmacokinetics (PK) between obese and non-obese 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 standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies for providing steady-state concentrations (C(ss)) 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) and 52 kg (16–164), respectively. The majority (94%) of children were obese. A two-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 mcg/kg/h was associated with probabilities between 49% and 58% for achieving C(ss) within target; however, the risk of achieving C(ss) >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 C(ss) 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 C(ss) in children of varying weights.