Population pharmacokinetic analysis of dexmedetomidine in children using real-world data from electronic health records and remnant specimens.
Br J Clin Pharmacol
; 88(6): 2885-2898, 2022 06.
Article
in En
| MEDLINE
| ID: mdl-34957589
ABSTRACT
AIMS:
Our objectives were to perform a population pharmacokinetic analysis of dexmedetomidine in children using remnant specimens and electronic health records (EHRs) and explore the impact of patient's characteristics and pharmacogenetics on dexmedetomidine clearance.METHODS:
Dexmedetomidine dosing and patient data were gathered from EHRs and combined with opportunistically sampled remnant specimens. Population pharmacokinetic models were developed using nonlinear mixed-effects modelling. Stage 1 developed a model without genotype variables; Stage 2 added pharmacogenetic effects.RESULTS:
Our final study population included 354 post-cardiac surgery patients aged 0-22 years (median 16 mo). The data were best described with a 2-compartment model with allometric scaling for weight and Hill maturation function for age. Population parameter estimates and 95% confidence intervals were 27.3 L/h (24.0-31.1 L/h) for total clearance, 161 L (139-187 L) for central compartment volume of distribution, 26.0 L/h (22.5-30.0 L/h) for intercompartmental clearance and 7903 L (5617-11 119 L) for peripheral compartment volume of distribution. The estimate for postmenstrual age when 50% of adult clearance is achieved was 42.0 weeks (41.5-42.5 weeks) and the Hill coefficient estimate was 7.04 (6.99-7.08). Genotype was not statistically or clinically significant.CONCLUSION:
Our study demonstrates the use of real-world EHR data and remnant specimens to perform a population pharmacokinetic analysis and investigate covariate effects in a large paediatric population. Weight and age were important predictors of clearance. We did not find evidence for pharmacogenetic effects of UGT1A4 or UGT2B10 genotype or CYP2A6 risk score.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dexmedetomidine
/
Cardiac Surgical Procedures
Type of study:
Prognostic_studies
Limits:
Adult
/
Child
/
Humans
Language:
En
Journal:
Br J Clin Pharmacol
Year:
2022
Document type:
Article
Affiliation country:
United States