{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T14:06:04Z","timestamp":1779458764582,"version":"3.53.1"},"reference-count":132,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Spanish Foundation of Hospital Pharmacy","award":["AG02.23003"],"award-info":[{"award-number":["AG02.23003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objective: Childhood obesity induces physiological changes that alter drug distribution and clearance; however, these patients are often excluded from clinical trials, creating a critical safety gap for high-alert medications (HAM). The Objective was to evaluate HAM dosing strategies and pharmacokinetic (PK) alterations in overweight and obese pediatric patients. Methods: A systematic review was conducted and registered in PROSPERO (CRD42023452126). A search of MEDLINE, EMBASE, Web of Science, and Cochrane CENTRAL (1990\u2013March 2026) identified studies reporting dosing strategies or PK of HAM in obese or overweight pediatric patients. Studies were included if they reported dosing recommendations or PK parameters. Eligible designs comprised prospective and retrospective, randomized and non-randomized, observational (cohort, case-control, and cross-sectional), case series, case reports, and narrative and systematic reviews. Study selection, data extraction, and quality assessment were conducted independently by two reviewers. Methodological quality was assessed using validated tools, and results were synthesized qualitatively. Results: Of 5801 records, 91 studies were included, providing evidence for only 27% of the evaluated HAM. Total body weight (TBW) appeared to be appropriate for insulin and vancomycin, although close monitoring was required. TBW-based dosing was associated with approximately 20% overexposure for enoxaparin, supporting the use of fat-free mass (FFM) or reduced dosing strategies. Increased clearance may justify higher doses for amlodipine and consideration of adult-equivalent dosing for metformin in adolescents. For gentamicin, FFM appeared to be the most appropriate descriptor, while adjusted body weight was used for valproic acid. In anesthetics and sedatives, reduced TBW-based dosing may be considered for propofol, whereas ideal body weight (IBW) or FFM were generally preferred for ketamine and dexmedetomidine. Analgesics such as fentanyl and morphine may require IBW- or FFM-based dosing, and maintenance dosing of paracetamol may require adjustment. Conclusions: Evidence remains limited and heterogeneous, with no standardized dosing approach. Model-informed strategies\u2014such as population PK (PopPK) and physiologically based PK model (PBPK) approaches\u2014may be useful for hypothesis generation and exploring PK variability; however, their clinical applicability is constrained by the limited and heterogeneous evidence base, and they should be considered exploratory.<\/jats:p>","DOI":"10.3390\/ph19050766","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dosing Strategies for High-Alert Medications in Obese Pediatric Patients: A Systematic Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-8728","authenticated-orcid":false,"given":"Yolanda","family":"Hern\u00e1ndez-Gago","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy, Insular Maternal and Child University Hospital Complex, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-5638","authenticated-orcid":false,"given":"Pedro J. Alcal\u00e1","family":"Minagorre","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Dr. Balmis University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-3686","authenticated-orcid":false,"given":"Jos\u00e9 Germ\u00e1n","family":"S\u00e1nchez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n Rodr\u00edguez","family":"Marrod\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Puerta de Hierro University Hospital, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hern\u00e1ndez Sabater","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Northwest Regional Hospital, 30400 Caravaca de la Cruz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Rodr\u00edguez","family":"Negr\u00edn","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Insular Maternal and Child University Hospital Complex, 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-7374","authenticated-orcid":false,"given":"Claudio-Alberto","family":"Rodr\u00edguez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Research Support Department, Insular Maternal and Child University Hospital Complex, 35016 Las Palmas de Gran Canaria, Spain"},{"name":"Nursing Department, Faculty of Healthcare Science, University of Las Palmas de Gran Canaria (ULPGC), 35016 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1001\/jamapediatrics.2024.1576","article-title":"Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis","volume":"178","author":"Zhang","year":"2024","journal-title":"JAMA Pediatr."},{"key":"ref_2","unstructured":"World Health Organization (2025, May 07). 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