Related Experiment Video
Updated: Jun 30, 2025
Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
Population pharmacokinetic analyses of methotrexate in pediatric patients: a systematic review
Yu Cheng1,2, Yujia Zhang1, Ying Zhang1
1Department of Pharmacy, Shengjing Hospital Affiliated to China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning Province, China.
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.
More Related Videos
08:38Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
08:46Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications
Published on: April 21, 2022
Related Concept Videos
01:12Analysis of Population Pharmacokinetic Data
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
01:02Noncompartmental Analysis: Mean Transit, Absorption and Dissolution Time
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area...
01:14Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
01:21Factors Affecting Drug Response: Overview