ArticleBritish journal of clinical pharmacology2006
Determinants of the elimination of methotrexate and 7-hydroxy-methotrexate following high-dose infusional therapy to cancer patients.
Article in British journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- A Systematic Review of Population Pharmacokinetic Models of Methotrexate.European journal of drug metabolism and pharmacokinetics · 2022Pooled it
- Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance.British journal of clinical pharmacology · 2014Trial
- Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.British journal of clinical pharmacology · 2012Trial
- Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: A pharmacokinetic-pharmacodynamic analysis from the IELSG no. 20 trial.British journal of cancer · 2010Trial
- 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
- GRK2 dysfunction mediates acute kidney injury in murine administered methotrexate combined with omeprazole.Acta pharmacologica Sinica · 2026Article
- Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice.EClinicalMedicine · 2025Review
- Effects of GLPG3970 on Sulfasalazine and Methotrexate Pharmacokinetics in Healthy Adults: Two Open-Label, Phase I, Drug-Drug Interaction Studies.Clinical pharmacology and therapeutics · 2025Article
- Population Pharmacokinetic and Toxicity Analysis of High-Dose Methotrexate in Patients with Central Nervous System Lymphoma.Clinical pharmacokinetics · 2025Article
- 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
- Impact of Methotrexate and 7-Hydroxymethotrexate Exposure on Renal Toxicity in Pediatric Non-Hodgkin Lymphoma.Cancer medicine · 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
- Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024Article
- Kidney Drug Transporters in Pharmacotherapy.International journal of molecular sciences · 2023Review
- Glucarpidase for Treating Adults with Delayed Methotrexate Elimination Due to Impaired Renal Function: An Economic Simulation Analysis.ClinicoEconomics and outcomes research : CEOR · 2023Article
- Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia.Frontiers in pharmacology · 2021Article
- Article
- Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.British journal of clinical pharmacology · 2020Article
- Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.The oncologist · 2018Article
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
aimsTo characterize determinants of the elimination of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) in patients receiving high-dose MTX therapy (HDMTX).
methods24 and 48-h blood samples from 76 patients receiving HDMTX (dose range 300 mg m-2 to 12 g m-2) were analysed, and concentration-time data were subjected to population pharmacokinetic and covariate analysis using nonlinear mixed-effect modelling (NONMEM).
resultsTreatment-related mortality was 1.3% (one patient with renal failure). Values for MTX clearance (CLMTX) and 7-OH-MTX clearance (CL7-OH-MTX) were estimated at 8.85 and 2 L-1, respectively. Baseline creatinine clearance correlated with CLMTX and CL7-OH-MTX. Concurrent administration of benzimidazoles led to a 27% decrease in CLMTX and a 39% decrease in CL7-OH-MTX. Prior administration of nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in a 16% decrease in CLMTX and a 38% decrease in CL7-OH-MTX. Plasma MTX concentrations were significantly higher in patients also receiving benzimidazoles at 24 h (2.01 micromol L-1vs. 0.66 micromol L-1, P<10(-4)) and at 48 h (0.25 micromol L-1vs. 0.12 micromol L-1, P<10(-4)). 7-OH-MTX plasma concentrations were also significantly higher in patients with concurrent benzimidazoles as compared with patients without benzimidazoles at 24 h (4.47 micromol L-1vs. 2.52 micromol L-1, P=0.0009) and at 48 h (1.11 micromol L-1vs. 0.72 micromol L-1, P=0.031).
conclusionsIn patients receiving HDMTX, concurrent administration of benzimidazoles was associated with a significant decrease of CLMTX and CL7-OH-MTX, resulting in significantly higher plasma concentrations of MTX and 7-OH-MTX. The data suggest that benzimidazole treatment should be seen as a relative contraindication for HDMTX.
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