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

Autor: Maharaj AR; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA., Wu H; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA., Zimmerman KO; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., Speicher DG; Division of Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA., Sullivan JE; University of Louisville, Kosair Charities Pediatric Clinical Research Unit, and Norton Children's Hospital, Louisville, Kentucky, USA., Watt K; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA., Al-Uzri A; Oregon Health and Science University, Portland, Oregon, USA., Payne EH; The Emmes Company, LLC, Rockville, Maryland, USA., Erinjeri J; The Emmes Company, LLC, Rockville, Maryland, USA., Lin S; The Emmes Company, LLC, Rockville, Maryland, USA., Harper B; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA., Melloni C; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA., Hornik CP; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2020 May; Vol. 60 (5), pp. 636-647. Date of Electronic Publication: 2019 Dec 08.
DOI: 10.1002/jcph.1562
Abstrakt: 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 (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 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 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.
(© 2019, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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