Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review.
Background and objectives: Methotrexate is widely utilized in the chemotherapy of malignant tumors and autoimmune diseases in the pediatric population, but dosing can be challenging. Several population pharmacokinetic models were developed to characterize factors influencing variability and improve...
| Published in: | European Journal of Clinical Pharmacology Vol. 80; no. 7; pp. 965 - 983 |
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| Main Authors: | , , , , |
| Format: | research systematic review tables/charts Journal Article |
| Published: |
Springer Nature
Jul2024
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=177714872&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 177714872 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jul2024 vid: 80 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 177714872 176094982 177714872 177714872 10.1007/s00228-024-03665-x 177714872 ppf: 965 ppct: 18 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review. aug: au: Cheng, Yu Zhang, Yujia Zhang, Ying Liu, Maobai Zhao, Limei affil: https://ror.org/00v408z34 Department of Pharmacy, Shengjing Hospital Affiliated to China Medical University, 36 Sanhao Street, 110004, Shenyang, Liaoning Province, China sug: subj: Methotrexate Pharmacokinetics Pediatric Care Drug Monitoring Human Systematic Review Funding Source PubMed Embase Checklists Models, Structural Body Size Kidney Physiology Drug Elimination Routes Polymorphism, Genetic Male Female Child Adolescence Descriptive Statistics Dose-Response Relationship, Drug Child: 6-12 years Adolescent: 13-18 years Male Female ab: Background and objectives: Methotrexate is widely utilized in the chemotherapy of malignant tumors and autoimmune diseases in the pediatric population, but dosing can be challenging. Several population pharmacokinetic models were developed to characterize factors influencing variability and improve individualization of dosing regimens. However, significant covariates included varied across studies. The primary objective of this review was to summarize and discuss population pharmacokinetic models of methotrexate and covariates that influence pharmacokinetic variability in pediatric patients. Methods: Systematic searches were conducted in the PubMed and EMBASE databases from inception to 7 July 2023. Reporting Quality was evaluated based on a checklist with 31 items. The characteristics of studies and information for model construction and validation were extracted, summarized, and discussed. Results: Eighteen studies (four prospective studies and fourteen retrospective studies with sample sizes of 14 to 772 patients and 2.7 to 93.1 samples per patient) were included in this study. Two-compartment models were the commonly used structural models for methotrexate, and the clearance range of methotrexate ranged from 2.32 to 19.03 L/h (median: 6.86 L/h). Body size and renal function were found to significantly affect the clearance of methotrexate for pediatric patients. There were limited reports on the role of other covariates, such as gene polymorphisms and co-medications, in the pharmacokinetic parameters of methotrexate pediatric patients. Internal and external evaluations were used to assess the performance of the population pharmacokinetic models. Conclusion: A more rigorous external evaluation needs to be performed before routine clinical use to select the appropriate PopPK model. Further research is necessary to incorporate larger cohorts or pool analyses in specific susceptible pediatric populations to improve the understanding of predicted exposure profiles and covariate identification. pubtype: Academic Journal doctype: research systematic review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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