{"id":678342,"date":"2026-11-08T05:30:12","date_gmt":"2026-11-08T05:30:12","guid":{"rendered":"https:\/\/www.newsbeep.com\/ie\/678342\/"},"modified":"2026-11-08T05:30:12","modified_gmt":"2026-11-08T05:30:12","slug":"parent-metabolite-pbpk-model-of-methotrexate-to-inform-pediatric-extrapolation-transporter-mediated-drug-drug-interactions-and-renal-impairment","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ie\/678342\/","title":{"rendered":"Parent-metabolite PBPK model of methotrexate to inform pediatric extrapolation, transporter-mediated drug\u2013drug interactions, and renal impairment"},"content":{"rendered":"

Hider, S. L., Bruce, I. N. & Thomson, W. The pharmacogenetics of methotrexate. Rheumatology 46, 859 (2007).<\/p>\n

Sl\u00f8rdal, L., Kolmannskog, S., Prytz, P. S., Moe, P. J. & Aarbakke, J. Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate after high-dose (33.6\u00a0g\/m2) methotrexate therapy. Pediatr. Hematol. Oncol. 3, 127\u2013134 (1986).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Maryam, H., Meenal, M. Methotrexate. National Library of Medicine (2024). https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK556114\/<\/a>.<\/p>\n

Nagamine, A. et al. Target concentration achievement for efficacy and safety of patients with osteosarcoma treated with high-dose methotrexate based on individual pharmacokinetics: a retrospective study. Oncol. Lett. 25, 70 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ramsey, L. B. et al. Consensus guideline for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance. Oncologist 23, 52\u201361 (2018).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Roth, M., Obaidat, A. & Hagenbuch, B. OATPs OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br. J. Pharmacol. 165, 1260\u20131287 (2012).<\/p>\n

Choughule, K. V., Joswig-Jones, C. A. & Jones, J. P. Interspecies differences in the metabolism of methotrexate: an insight into the active site differences between human and rabbit aldehyde oxidase. Biochem. Pharmacol. 96, 288\u2013295 (2015).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dervieux, T. et al. HPLC determination of thiopurine nucleosides and nucleotides in vivo in lymphoblasts following mercaptopurine therapy. Clin. Chem. 48, 61\u201368 (2002).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Grim, J., Chladek, J. & Martinkovi, J. Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases. Clin. Pharmacokinet. 42, 139\u2013151 (2003).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Prasad, B. et al. Ontogeny of hepatic drug transporters as quantified by LC-MS\/MS Proteomics. Clin. Pharmacol. Ther. 100, 362\u2013370 (2016).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dette, C. M. U. et al. Advancing rare disease therapeutics through digital twins: opportunities in drug development and precision dosing. Comput. Struct. Biotechnol. J. 28, 592\u2013608. https:\/\/doi.org\/10.1016\/j.csbj.2025.11.047<\/a> (2025).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Britz, H. et al. Physiologically based pharmacokinetic models of probenecid and furosemide to predict transporter mediated drug-drug interactions. Pharm. Res. 37, 250 (2020).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

European Medicines Agency: EMA\/CHMP\/458101\/2016 – Reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation (2019). https:\/\/www.ema.europa.eu\/en\/reporting-physiologically-based-pharmacokinetic-pbpk-modelling-simulation-scientific-guideline<\/a>.<\/p>\n

U.S. Food and Drug Administration: FDA-2016-D-3969 – Physiologically Based Pharmacokinetic Analyses \u2014 Format and Content Guidance for Industry (2018). https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/physiologically-based-pharmacokinetic-analyses-format-and-content-guidance-industry<\/a>.<\/p>\n

Wojtyniak, J., Britz, H., Selzer, D., Schwab, M. & Lehr, T. Data digitizing: accurate and precise data extraction for quantitative systems pharmacology and physiologically\u2010based pharmacokinetic modeling. CPT Pharmacometr. Syst. Pharmacol. 9, 322\u2013331. https:\/\/doi.org\/10.1002\/psp4.12511<\/a> (2020).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chemicalize Methotrexate Entry. https:\/\/chemicalize.com\/app\/calculation<\/a> (2026).<\/p>\n

Chen et al. Pubchem 2025 update. Nucleic Acids Res. (2025). https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/5484402#section=Chemical-and-Physical-Properties<\/a>.<\/p>\n

Chemicalize 7-Hydroxymethotrexate Entry. https:\/\/chemicalize.com\/app\/calculation<\/a> (2026).<\/p>\n

Uhl\u00e9n, M. et al. Tissue-based map of the human proteome. Science (1979) 347, 8596 (2015).<\/p>\n

Fisher, R. S., Rock, E. & Malmud, L. S. Effects of meal composition on gallbladder and gastric emptying in man. Dig. Dis. Sci. 32, 1337\u20131344 (1987).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Selzer, D., R\u00fcdesheim, S., Dette, C. M. U., Marok, F. Z. & Lehr, T. Ospgsa: global sensitivity analysis for open systems pharmacology models (2026). https:\/\/github.com\/Clinical-Pharmacy-Saarland-University\/ospgsa<\/a>.<\/p>\n

Borgonovo, E. A new uncertainty importance measure. Reliab. Eng. Syst. Saf. 92, 771\u2013784 (2007).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

De Carlo, A., Tosca, E. M., Melillo, N. & Magni, P. A two-stages global sensitivity analysis by using the \u03b4 sensitivity index in presence of correlated inputs: application on a tumor growth inhibition model based on the dynamic energy budget theory. J. Pharmacokinet. Pharmacodyn. 50, 395\u2013409 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cuquerella-Gilabert, M. et al. Leveraging two\u2010stage \u03b4 global sensitivity analysis method to inform parameter estimation in PBPK models. Pharm Stat 25, 859 (2026).<\/p>\n

Jamaladdin, N. et al. Key pharmacokinetic parameters of 74 pediatric anticancer drugs providing assistance in preclinical studies. Clin. Pharmacol. Ther. 114, 904\u2013913 (2023).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dong, W. C. et al. Simultaneous determination of unbound plasma concentration of methotrexate and 7-hydroxymethotrexate in children patients receiving high-dose methotrexate therapy. Drug Des. Devel Ther. 19, 4383\u20134396. https:\/\/doi.org\/10.2147\/DDDT.S516431<\/a> (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hunt, J. P. et al. Maximum likelihood estimation of renal transporter ontogeny profiles for pediatric PBPK modeling. CPT Pharmacometr. Syst. Pharmacol. 13, 576\u2013588 (2024).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Open Systems Pharmacology Suite Community. PK-Sim\u00ae Ontogeny Database Documentation, Version 7.3 (2024). https:\/\/github.com\/Open-Systems-Pharmacology\/OSPSuite.Documentation\/blob\/master\/PK-Sim%20Ontogeny%20Database%20Version%207.3.pdf<\/a>.<\/p>\n

Namour, F. et al. Pharmacokinetics, safety, and tolerability of GLPG0259, a Mitogen-Activated Protein Kinase-Activated Protein Kinase 5 (MAPKAPK5) inhibitor, given as single and multiple doses to healthy male subjects. Drugs R D. 12, 141\u2013163. https:\/\/doi.org\/10.2165\/11633120-000000000-00000<\/a> (2012).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Stoller, G. R., Samuel, A. J., James, C. D., Robert, J. L. & Bruce, A. C. Pharmacokinetics of high-dose methotrexate (NSC-740). Rep. Div. Cancer Treat. NCI. 2, 285\u2013290 (1976).<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

U.S. Food and Drug Administration: FDA-2010-D-0133 – Pharmacokinetics in Patients with Impaired Renal Function \u2014 Study Design, Data Analysis, and Impact on Dosing 8 (2024). https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pharmacokinetics-patients-impaired-renal-function-study-design-data-analysis-and-impact-dosing<\/a>.<\/p>\n

Guest, E. J., Aarons, L., Houston, J. B., Rostami-Hodjegan, A. & Galetin, A. Critique of the two-fold measure of prediction success for ratios: application for the assessment of drug-drug interactions. Drug Metab. Dispos. 39, 170\u2013173 (2011).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rajagopalan, P. T. R. et al. Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics. Proc. Natl. Acad. Sci. U S A. 99, 13481 (2002).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jones, H. & Rowland-Yeo, K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacometrics Syst. Pharmacol. 2, 1\u201312 (2013).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schaller, S. et al. Evaluation of BCRP-related DDIs between methotrexate and cyclosporin A using physiologically based pharmacokinetic modelling. Drugs R D. 25, 1\u201317. https:\/\/doi.org\/10.1007\/s40268-024-00495-1<\/a> (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hwang, S. et al. Comprehensive evaluation of OATP- and BCRP\u2010mediated drug\u2013drug interactions of methotrexate using physiologically\u2010based pharmacokinetic modeling. Clin. Pharmacol. Ther. 116, 1013\u20131022 (2024).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Aherne, G. W., Piall, E., Marks, V., Mould, G. & White, W. F. Prolongation and enhancement of serum methotrexate concentrations by probenecid. BMJ 1, 1097\u20131099 (1978).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tracy, T. S. et al. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur. J. Clin. Pharmacol. 42, 121\u2013125 (1992).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Servier Medical Art by Servier is licensed under a Creative Commons Attribution 4.0 Unported License. https:\/\/creativecommons.org\/licenses\/by\/4.0\/<\/a> (2026).<\/p>\n

Skibi\u0144ska, L., Ramlau, C., Za\u0142uski, J. & Olejniczak, B. Methotrexate binding to human plasma proteins. Pol. J. Pharmacol. Pharm. 42, 151\u2013157 (1990).<\/p>\n

PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sl\u00f8rdal, L., Sager, G., J\u00e6ger, R. & Aarbakke, J. Interactions with the protein binding of 7-hydroxy-methotrexate in human serum in vitro. Biochem. Pharmacol. 37, 607\u2013611 (1988).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yousefi, G., Foroutan, S. M., Zarghi, A. & Shafaati, A. Synthesis and characterization of methotrexate polyethylene glycol esters as a drug delivery system. Chem. Pharm. Bull. (Tokyo). 58, 147\u2013153 (2010).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mir, O. et al. Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma. Cancer Chemother. Pharmacol. 66, 1059\u20131063 (2010).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chen, Z. S. et al. Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res. 63, 4048\u20134054 (2003).<\/p>\n

CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Inoue, K. & Yuasa, H. Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab. Pharmacokinet. 29, 12\u201319 (2014).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Patik, I. et al. Functional expression of the 11 human Organic Anion Transporting Polypeptides in insect cells reveals that sodium fluorescein is a general OATP substrate. Biochem. Pharmacol. 98, 649\u2013658 (2015).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ifergan, I., Jansen, G. & Assaraf, Y. G. The Reduced Folate Carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. J. Biol. Chem. 283, 20687\u201320695. https:\/\/doi.org\/10.1074\/jbc.M802812200<\/a> (2008).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Bedoui, Y. et al. Methotrexate an old drug with new tricks. Int. J. Mol. Sci. 20, 5023. https:\/\/doi.org\/10.3390\/ijms20205023<\/a> (2019).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Tanaka, G. & Kawamura, H. Anatomical and physiological characteristics for Asian reference man: Male and female of different ages: Tanaka model. Report Number: NIRS-M-115. In Division of Radioecology, National Institute of Radiological Sciences. Hitachinaka 311\u2009\u2013\u200912 Japan. (1996).<\/p>\n

Valentin, J. Basic anatomical and physiological data for use in radiological protection: reference values. Ann. ICRP. 32, 1\u2013277 (2002).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

National Center for Health Statistics. Third National Health and Nutrition Examination Survey, (NHANES III) (1997). https:\/\/wwwn.cdc.gov\/nchs\/nhanes\/nhanes3\/default.aspx<\/a>.<\/p>\n

Ishii, E. et al. Oral mucositis and salivary methotrexate concentration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia. Med. Pediatr. Oncol. 17, 429\u2013432 (1989).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ylinen, E., Jahnukainen, K., Saarinen-Pihkala, U. M. & Jahnukainen, T. Assessment of renal function during high-dose methotrexate treatment in children with acute lymphoblastic leukemia. Pediatr. Blood Cancer. 61, 2199\u20132202. https:\/\/doi.org\/10.1002\/pbc.25137<\/a> (2014).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Winograd, B. et al. Renal excretion and pharmacokinetics of methotrexate and 7-hydroxy-methotrexate following a 24-h high dose infusion of methotrexate in children. Eur. J. Clin. Pharmacol. 30, 231\u2013238 (1986).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kearney, P. J., Light, P. A., Preece, A. & Mott, M. G. Unpredictable serum levels after oral methotrexate in children with acute lymphoblastic leukaemia. Cancer Chemother. Pharmacol. 3, 859 (1979).<\/p>\n

Peters, S. A. & Dolgos, H. Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) models and overcoming some of the challenges to meeting them. Clin. Pharmacokinet. 58, 1355\u20131371 (2019).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Taylor, Z. L. et al. Systematic review of pharmacogenetic factors that influence high-dose methotrexate pharmacokinetics in pediatric malignancies. Cancers (Basel). 13, 2837. https:\/\/doi.org\/10.3390\/cancers13112837<\/a> (2021).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hutzler, J. M., Yang, Y. S., Brown, C., Heyward, S. & Moeller, T. Aldehyde oxidase activity in donor-matched fresh and cryopreserved human hepatocytes and assessment of variability in 75 donors. Drug Metab. Dispos. 42, 1090\u20131097 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Foti, A., Dorendorf, F. & Leimk\u00fchler, S. A single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase. PLoS One. 12, e0182061. https:\/\/doi.org\/10.1371\/journal.pone.0182061<\/a> (2017).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ogungbenro, K. & Aarons, L. Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 1: methotrexate The CRESim & Epi-CRESim Project Groups. J. Pharmacokinet. Pharmacodyn. 41, 159\u2013171. https:\/\/doi.org\/10.1007\/s10928-014-9354-4<\/a> (2026).<\/p>\n

Le Merdy, M., Mullin, J. & Lukacova, V. Development of PBPK model for intra-articular injection in human: methotrexate solution and rheumatoid arthritis case study. J. Pharmacokinet. Pharmacodyn. 48, 909\u2013922 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Brandhonneur, N., Noury, F., Bruy\u00e8re, A., Saint-Jalmes, H. & Le Corre, P. PBPK model of methotrexate in cerebrospinal fluid ventricles using a combined microdialysis and MRI acquisition. Eur. J. Pharm. Biopharm. 104, 117\u2013130 (2016).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Batey, M. A. et al. Population pharmacokinetics of adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Eur. J. Cancer. 38, 1081\u20131089 (2002).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Campagne, O. et al. Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors. Eur. J. Pharm. Sci. 193, 106669 (2024).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fukuhara, K., Ikawa, K., Morikawa, N. & Kumagai, K. Population pharmacokinetics of high-dose methotrexate in Japanese adult patients with malignancies: a concurrent analysis of the serum and urine concentration data. J. Clin. Pharm. Ther. 33, 677\u2013684 (2008).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Korell, J. et al. A Population pharmacokinetic model for low-dose methotrexate and its polyglutamated metabolites in red blood cells. Clin. Pharmacokinet. 52, 475\u2013485 (2013).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pesenti, G., Foppoli, M. & Manca, D. A minimal physiologically based pharmacokinetic model for high-dose methotrexate. Cancer Chemother. Pharmacol. 88, 595\u2013606. https:\/\/doi.org\/10.1007\/s00280-021-04305-2<\/a> (2021).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mould, D. & Upton, R. Basic concepts in population modeling, simulation, and model-based drug development\u2014part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst. Pharmacol. 2, 1\u201314 (2013).<\/p>\n

Article<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Darwich, A. S. Model-informed precision dosing: background, requirements, validation, implementation, and forward trajectory of individualizing drug therapy. Annu. Rev. Pharmacol. Toxicol. 61, 225\u2013245 (2021).<\/p>\n

Article<\/a>\u00a0
\n CAS<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n","protected":false},"excerpt":{"rendered":"Hider, S. L., Bruce, I. N. & Thomson, W. The pharmacogenetics of methotrexate. Rheumatology 46, 859 (2007). Sl\u00f8rdal,…\n","protected":false},"author":2,"featured_media":678343,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[33],"tags":[287207,38733,2877,103,2026,61,60,521,371,194835,2027,150877,287208,287206,82],"class_list":["post-678342","post","type-post","status-publish","format-standard","has-post-thumbnail","category-medication","tag-7-hydroxymethotrexate","tag-computational-biology-and-bioinformatics","tag-drug-discovery","tag-health","tag-humanities-and-social-sciences","tag-ie","tag-ireland","tag-medical-research","tag-medication","tag-methotrexate","tag-multidisciplinary","tag-ontogeny","tag-pediatric-scaling","tag-physiologically-based-pharmacokinetic-pbpk-modeling","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/678342","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=678342"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/678342\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/678343"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=678342"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=678342"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=678342"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}