{"doi":"10.1002/jcph.70143","title":"Population Pharmacokinetics to Support Intravenous and Enteral Methadone Dosing in Children","abstract":"Methadone is used in hospitalized children to treat pain and iatrogenic opiate withdrawal. Optimal pediatric dosing for both enteral and intravenous methadone is unknown. We conducted two prospective, multi-center, open-label studies to characterize the pharmacokinetics of methadone in the pediatric population. These studies were conducted at a total of 23 US children's hospitals. Ninety-nine children with a median (range) age of 2.3 (0-19.0) years and weight of 13.0 (0.72-159) kg were prescribed methadone per standard of care for treatment of pain or iatrogenic opiate withdrawal. Ninety-nine children received median (range) methadone doses of 0.11 (0.01-0.39) mg/kg intravenously and 0.10 (0.01-0.61) mg/kg enterally. Ten participants received only intravenous doses; 78 received only enteral doses; and 11 received intravenous and enteral doses. We analyzed 263 pharmacokinetic samples with a median (range) methadone plasma concentration of 42.2 (0.9-729.2) ng/mL. A one-compartment population pharmacokinetic model described the methadone data well. Median (range) empiric Bayesian estimates of clearance, volume of distribution, and half-life were 0.17 (0.009-1.50) L/h/kg, 4.99 (0.97-20.6) L/kg, and 20.5 (3.0-86.2) h, respectively. Dosing simulations showed that doses of 0.1 mg/kg every 8 h (intravenous) and 0.2 mg/kg every 8 h (enteral) achieved exposures associated with pain control and reduction in withdrawal symptoms. Based on observed exposures and model simulations, we recommend a starting dose of 0.1 mg/kg intravenous or 0.2 mg/kg enterally (max 10 mg) every 8 h. Because of wide interindividual variability, this dose should be titrated to effect.","journal":"The Journal of Clinical Pharmacology","year":2025,"id":549832,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9134,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1445172,"name":"ES Thompson","orcid":null,"position":1,"is_corresponding":false},{"id":1444550,"name":"Lisa H. Lam","orcid":"0000-0001-5188-9522","position":2,"is_corresponding":false},{"id":1301533,"name":"Kanecia Zimmerman","orcid":null,"position":3,"is_corresponding":false},{"id":333627,"name":"Christoph P. Hornik","orcid":"0000-0001-7056-8759","position":4,"is_corresponding":false},{"id":356104,"name":"Andrew M. Atz","orcid":"0000-0002-4744-3832","position":5,"is_corresponding":false},{"id":1445173,"name":"A. Sevilla Fernandez","orcid":null,"position":6,"is_corresponding":false},{"id":602721,"name":"Susan R. Hupp","orcid":null,"position":7,"is_corresponding":false},{"id":342567,"name":"Varsha Bhatt‐Mehta","orcid":"0000-0003-0085-421X","position":8,"is_corresponding":false},{"id":155018,"name":"Daniel K. Benjamin","orcid":null,"position":9,"is_corresponding":false},{"id":488936,"name":"Ravinder Anand","orcid":"0000-0001-8628-2130","position":10,"is_corresponding":false},{"id":333631,"name":"Michael Cohen‐Wolkowiez","orcid":"0000-0002-2458-2266","position":11,"is_corresponding":false},{"id":1445174,"name":"Daniel Gonzalez","orcid":null,"position":12,"is_corresponding":false},{"id":155015,"name":"P. Brian Smith","orcid":null,"position":13,"is_corresponding":false},{"id":330622,"name":"Edmund V. Capparelli","orcid":"0000-0002-1630-0505","position":14,"is_corresponding":false},{"id":401783,"name":"Kevin Watt","orcid":"0000-0002-5975-5091","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41474167","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":[]}