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1000
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Abstract/Summary
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Background!#!The aim of this study was to identify sources of variability including patient gender and body surface area (BSA) in pharmacokinetic (PK) exposure for high-dose methotrexate (MTX) continuous infusion in a large cohort of patients with hematological and solid malignancies.!##!Methods!#!We conducted a retrospective PK analysis of MTX plasma concentration data from hematological/oncological patients treated at the University Hospital of Cologne between 2005 and 2018. Nonlinear mixed effects modeling was performed. Covariate data on patient demographics and clinical chemistry parameters was incorporated to assess relationships with PK parameters. Simulations were conducted to compare exposure and probability of target attainment (PTA) under BSA adjusted, flat and stratified dosing regimens.!##!Results!#!Plasma concentration over time data (2182 measurements) from therapeutic drug monitoring from 229 patients was available. PK of MTX were best described by a three-compartment model. Values for clearance (CL) of 4.33 [2.95-5.92] L h!##!Conclusion!#!A dosing scheme with doses stratified across BSA quartiles is suggested to optimize target exposure attainment. Influence of patient sex on CL of MTX is present but small in magnitude.
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1000
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Hinweis
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DeepGreen-ID: 1e8a89dd26dd4740a6419cd148322320 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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