{"doi":"10.1111/bcp.15194","title":"Population pharmacokinetic analysis of dexmedetomidine in children using real‐world data from electronic health records and remnant specimens","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.","journal":"British Journal of Clinical Pharmacology","year":2021,"id":191518,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5112,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":337055,"name":"Joseph H. Breeyear","orcid":"0000-0002-6179-0515","position":1,"is_corresponding":false},{"id":232779,"name":"Richard M. Caprioli","orcid":"0000-0001-5859-3310","position":2,"is_corresponding":false},{"id":337054,"name":"Todd L. Edwards","orcid":"0000-0003-4318-6119","position":3,"is_corresponding":false},{"id":757843,"name":"Brian Hachey","orcid":null,"position":4,"is_corresponding":false},{"id":404969,"name":"Prince J. Kannankeril","orcid":"0000-0002-1529-9872","position":5,"is_corresponding":false},{"id":279178,"name":"Jacob M. Keaton","orcid":"0000-0002-6371-7530","position":6,"is_corresponding":false},{"id":757844,"name":"Matthew D. Marshall","orcid":null,"position":7,"is_corresponding":false},{"id":235375,"name":"Sara L. Van Driest","orcid":"0000-0003-2580-1405","position":8,"is_corresponding":false},{"id":459735,"name":"Leena Choi","orcid":"0000-0002-2544-7090","position":9,"is_corresponding":false},{"id":482641,"name":"Nathan T. James","orcid":"0000-0001-7079-9151","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:49:35.285023Z","pmid":"34957589","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}