{"doi":"10.1007/s40262-023-01285-9","title":"Pharmacokinetics of Oral Vitamin D in Children with Obesity and Asthma","abstract":"BACKGROUND AND OBJECTIVE: Vitamin D insufficiency is common in several pediatric diseases including obesity and asthma. Little data exist describing the pharmacokinetics of oral vitamin D in children or the optimal dosing to achieve therapeutic 25(OH)D targets. Describe the pharmacokinetics of oral Vitamin D in children with asthma. METHODS: This was a multi-center, randomized, open-label, oral supplementation study to describe the pharmacokinetics of vitamin D in children aged 6-17 years who have asthma and were overweight/obese. Participants had a serum 25(OH)D concentration between 10 and < 30 ng/mL at baseline. In Part 1 of the study, we assessed four 16-week dosing regimens for their ability to achieve 25(OH)D concentrations ≥ 40 ng/mL. Using serial serum 25(OH)D sampling over 28 weeks, we created a population pharmacokinetic model and performed dosing simulations to achieve 25(OH)D concentrations ≥ 40 ng/mL. In Part 2, the optimal regimen chosen from Part 1 was compared (2:1) to a standard-of-care control dose (600 international units [IU] daily) over 16 weeks. A final population pharmacokinetic model using both parts was developed to perform dosing simulations and determine important co-variates in the pharmacokinetics of vitamin D. RESULTS: Based on empiric and simulation data, the daily dose of 8000 IU and a loading dose of 50,000 IU were chosen; this regimen raised 25(OH)D concentrations above 40 ng/mL in the majority of participants while avoiding concentrations > 100 ng/mL. A 50,000-IU loading dose led to faster achievement of 25(OH)D therapeutic concentrations (≥ 40 ng/mL). The estimated median (5th-95th percentiles) apparent clearance of vitamin D from the final population pharmacokinetic model was 0.181 (0.155-0.206) L/h. The body mass index z-score was a significant covariate on apparent clearance and was associated with a significantly decreased median half-life in 25(OH)D (body mass index z-score 1.00-1.99: 97.7 days, body mass index z-score 2.00-2.99: 65.9 days, body mass index z-score ≥ 3.00: 39.1 days, p < 0.001). CONCLUSIONS: Obesity impacts vitamin D clearance and the half-life, but serum concentrations > 40 ng/mL can be reached in most children using a loading dose of 50,000 IU followed by a daily dose of 8000 IU. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT03686150.","journal":"Clinical Pharmacokinetics","year":2023,"id":366007,"datarank":0.418451843609834,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.126565321251537,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.126565321251537,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9396,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03686150"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1122225,"name":"Rodrigo Gonzalez Ramirez","orcid":null,"position":1,"is_corresponding":false},{"id":333628,"name":"Stephen J. Balevic","orcid":"0000-0002-4016-1680","position":2,"is_corresponding":false},{"id":497735,"name":"Scott Bickel","orcid":"0000-0002-0940-3063","position":3,"is_corresponding":false},{"id":333627,"name":"Christoph P. Hornik","orcid":"0000-0001-7056-8759","position":4,"is_corresponding":false},{"id":498508,"name":"Joseph M. Majure","orcid":null,"position":5,"is_corresponding":false},{"id":1122226,"name":"Saranya Venkatachalam","orcid":null,"position":6,"is_corresponding":false},{"id":356109,"name":"Jessica Snowden","orcid":"0000-0002-0715-151X","position":7,"is_corresponding":false},{"id":295540,"name":"Brian O’Sullivan","orcid":"0000-0001-8887-843X","position":8,"is_corresponding":false},{"id":342566,"name":"Laura P. James","orcid":"0000-0002-4266-3924","position":9,"is_corresponding":false},{"id":409652,"name":"Jason E. Lang","orcid":"0000-0001-9115-5312","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T01:14:50.885797Z","pmid":"37646988","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":[]}