Trial reportClinical pharmacokinetics2002
Bayesian estimation of methotrexate pharmacokinetic parameters and area under the curve in children and young adults with localised osteosarcoma.
Trial report in Clinical pharmacokinetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 42 citations in OpenAlex.
- Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukaemia.Clinical pharmacokinetics · 2006Trial
- A Model-Informed Early Prediction of Methotrexate-Induced Acute Kidney Injury in Pediatric Patients with Osteosarcoma Using Real-World Data: A Multi-center Pharmacokinetic Study.Clinical pharmacokinetics · 2026Article
- Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model.Pharmaceutics · 2024Article
- Evaluation of body-surface-area adjusted dosing of high-dose methotrexate by population pharmacokinetics in a large cohort of cancer patients.BMC cancer · 2021Article
- The Population Pharmacokinetics of High-Dose Methotrexate in Infants with Acute Lymphoblastic Leukemia Highlight the Need for Bedside Individualized Dose Adjustment: A Report from the Children's Oncology Group.Clinical pharmacokinetics · 2019Article
- Early phase and adaptive design clinical trials in rheumatoid arthritis: a systematic review of early phase trials.Rheumatology advances in practice · 2018Article
- Population pharmacokinetics of high-dose methotrexate after intravenous administration in Chinese osteosarcoma patients from a single institution.Chinese medical journal · 2015Article
- Impact of ABCC2 polymorphisms on high-dose methotrexate pharmacokinetics in patients with lymphoid malignancy.The pharmacogenomics journal · 2013Article
- Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma.European journal of clinical pharmacology · 2011Article
- Evaluating performance of a decision support system to improve methotrexate pharmacotherapy in children and young adults with cancer.Therapeutic drug monitoring · 2011Article
- Clinical pharmacology in the adolescent oncology patient.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Review
- Integration of modeling and simulation into hospital-based decision support systems guiding pediatric pharmacotherapy.BMC medical informatics and decision making · 2008Article
- Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology.Clinical pharmacokinetics · 2008Review
- Risk Factors for Delayed Elimination of Methotrexate in Children, Adolescents and Young Adults With Osteosarcoma.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate is the most efficient anticancer drug in osteosarcoma. It requires individual exposure monitoring because of the high doses used, its wide interpatient pharmacokinetic variability and the existence of demonstrated relationships between efficacy, toxicity and serum drug concentrations.
objectiveTo develop a maximum a posteriori (MAP) Bayesian estimator able to predict individual pharmacokinetic parameters and exposure indices such as area under the curve (AUC) for methotrexate from a few blood samples, in order to prevent toxicity and facilitate further studies of the relationships between efficacy and exposure.
methodsMethotrexate population pharmacokinetics were estimated by a retrospective analysis of concentration data from 40 children and young adults by using the nonparametric expectation maximisation method NPEM. A linear two-compartment model with elimination from the central compartment was assumed. Individual pharmacokinetic parameters and AUC were subsequently estimated in 30 other young patients, using MAP Bayesian estimation as implemented in two programs, ADAPT II and an inhouse program Winphar((R)).
resultsThe pharmacokinetic parameters used in the model were the volume of the central compartment (V(1)) and the transfer constants (k(10), k(12) and k(21)). The mean values (with percentage coefficient of variation) obtained were: 18.24L (54.1%) and 0.41 (42.3%), 0.0168 (68.7%), and 0.1069 (61.3%) h(-1), respectively. Bayesian forecasting enabled nonbiased estimation of AUC and systemic clearance using a schedule with two sampling times (6 and 24 hours after the beginning of the infusion) and either program. Collection of a third sample at 4 hours improved the precision.
conclusionThe Bayesian adaptive method developed herein allows accurate estimation of individual exposure to methotrexate and can easily be used in clinical practice.
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