ArticleChinese medical journal2015
Population pharmacokinetics of high-dose methotrexate after intravenous administration in Chinese osteosarcoma patients from a single institution.
Article in Chinese medical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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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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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Factors influencing methotrexate pharmacokinetics highlight the need for individualized dose adjustment: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- A Systematic Review of Population Pharmacokinetic Models of Methotrexate.European journal of drug metabolism and pharmacokinetics · 2022Pooled it
- Population pharmacokinetic model of high-dose methotrexate in Malaysian adults with hematological malignancies.European journal of clinical pharmacology · 2026Article
- Population pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.Frontiers in pharmacology · 2025Article
- Population pharmacokinetic model of high-dose methotrexate in Chinese patients with intracranial germ cell tumors.Frontiers in pharmacology · 2025Article
- An interactive dose optimizer based on population pharmacokinetic study to guide dosing of methotrexate in Chinese patients with osteosarcoma.Cancer chemotherapy and pharmacology · 2024Article
- Anticipating Leucovorin Rescue Therapy in Patients with Osteosarcoma through Methotrexate Population Pharmacokinetic Model.Pharmaceutics · 2024Article
- External Evaluation of Population Pharmacokinetic Models of Methotrexate for Model-Informed Precision Dosing in Pediatric Patients with Acute Lymphoid Leukemia.Pharmaceutics · 2023Article
- Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy.Aging · 2022Article
- Urine volume to hydration volume ratio is associated with pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma.Pharmacology research & perspectives · 2021Observational
- Evaluation of body-surface-area adjusted dosing of high-dose methotrexate by population pharmacokinetics in a large cohort of cancer patients.BMC cancer · 2021Article
- S-phase kinase-associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells.International journal of oncology · 2018Article
- The pharmacokinetics of high-dose methotrexate in people living with HIV on antiretroviral therapy.Cancer chemotherapy and pharmacology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition.
methodsAn intravenous HD-MTX solution (10 g/m 2 ) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained.
resultsThe following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1 ) = CL1TV × [1 - θ CL1- MTXNUM × MTXNUM] × [1 - θ CL1- CrCl1 × (CrCl1 - 1.89)] × e ηCL1i (L/h). V1 (central volume): (V1)i = V1TV × e ηV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV × [1 - θCL2 - BODY AREA × (body area - 1.62)] × e ηCL2i (L/h). V2 (peripheral compartment): (V2 )i = V2TV × [1 - θ V2-bodyarea × (bodyarea-1.62)] × e ηV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL1, and body surface area had a significant effect on the CL2 and the V2 (P < 0. 01).
conclusionsA good fit was derived for the PPK. The model could be used to provide guidance for MTX treatment and reduce adverse effects.
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