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Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma
High‐dose methotrexate (HD‐MTX)‐based chemotherapy is the first‐line treatment for primary central nervous system lymphoma (PCNSL), but is associated with severe adverse effects, including myelosuppression and renal impairment. MTX is primarily excreted by the kidneys. Renal function calculated usin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525095/ https://www.ncbi.nlm.nih.gov/pubmed/34664791 http://dx.doi.org/10.1002/prp2.883 |
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author | Isono, Tetsuichiro Hira, Daiki Morikochi, Aya Fukami, Tadateru Ueshima, Satoshi Nozaki, Kazuhiko Terada, Tomohiro Morita, Shin‐ya |
author_facet | Isono, Tetsuichiro Hira, Daiki Morikochi, Aya Fukami, Tadateru Ueshima, Satoshi Nozaki, Kazuhiko Terada, Tomohiro Morita, Shin‐ya |
author_sort | Isono, Tetsuichiro |
collection | PubMed |
description | High‐dose methotrexate (HD‐MTX)‐based chemotherapy is the first‐line treatment for primary central nervous system lymphoma (PCNSL), but is associated with severe adverse effects, including myelosuppression and renal impairment. MTX is primarily excreted by the kidneys. Renal function calculated using serum creatinine (Scr) derived from muscle may be overestimated in elderly PCNSL patients. Therefore, we aimed to construct a population pharmacokinetic model in PCNSL patients and explore the factors associated with MTX clearance. Sixteen PCNSL patients (median age, 66 years) treated with HD‐MTX were included, and serum MTX concentrations were measured at 193 points in 49 courses. A population pharmacokinetic analysis was performed using NONMEM. A Monte Carlo simulation was conducted, in which serum MTX concentrations were stratified into three groups of creatine clearance (Ccr) (50, 75, and 100 ml/min) with three groups of the urine volume to hydration volume (UV/HV) ratio (<1, 1–2, and >2). The final model was constructed as follows: MTX clearance = 4.90·(Ccr/94.5)(0.456)·(UV/HV)(0.458). In the Monte Carlo simulation, serum MTX concentrations were below the standard values (10, 1, and 0.1 µM at 24, 48, and 72 h, respectively, after the start of the MTX administration) in most patients with UV/HV >2, even with Ccr of 50 ml/min. Conversely, half of the patients with UV/HV <1 and Ccr of 50 ml/min failed to achieve the standard values. The present results demonstrated that the UV/HV ratio was useful for describing the pharmacokinetics of MTX in PCNSL patients. |
format | Online Article Text |
id | pubmed-8525095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85250952021-10-26 Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma Isono, Tetsuichiro Hira, Daiki Morikochi, Aya Fukami, Tadateru Ueshima, Satoshi Nozaki, Kazuhiko Terada, Tomohiro Morita, Shin‐ya Pharmacol Res Perspect Original Articles High‐dose methotrexate (HD‐MTX)‐based chemotherapy is the first‐line treatment for primary central nervous system lymphoma (PCNSL), but is associated with severe adverse effects, including myelosuppression and renal impairment. MTX is primarily excreted by the kidneys. Renal function calculated using serum creatinine (Scr) derived from muscle may be overestimated in elderly PCNSL patients. Therefore, we aimed to construct a population pharmacokinetic model in PCNSL patients and explore the factors associated with MTX clearance. Sixteen PCNSL patients (median age, 66 years) treated with HD‐MTX were included, and serum MTX concentrations were measured at 193 points in 49 courses. A population pharmacokinetic analysis was performed using NONMEM. A Monte Carlo simulation was conducted, in which serum MTX concentrations were stratified into three groups of creatine clearance (Ccr) (50, 75, and 100 ml/min) with three groups of the urine volume to hydration volume (UV/HV) ratio (<1, 1–2, and >2). The final model was constructed as follows: MTX clearance = 4.90·(Ccr/94.5)(0.456)·(UV/HV)(0.458). In the Monte Carlo simulation, serum MTX concentrations were below the standard values (10, 1, and 0.1 µM at 24, 48, and 72 h, respectively, after the start of the MTX administration) in most patients with UV/HV >2, even with Ccr of 50 ml/min. Conversely, half of the patients with UV/HV <1 and Ccr of 50 ml/min failed to achieve the standard values. The present results demonstrated that the UV/HV ratio was useful for describing the pharmacokinetics of MTX in PCNSL patients. John Wiley and Sons Inc. 2021-10-19 /pmc/articles/PMC8525095/ /pubmed/34664791 http://dx.doi.org/10.1002/prp2.883 Text en © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Isono, Tetsuichiro Hira, Daiki Morikochi, Aya Fukami, Tadateru Ueshima, Satoshi Nozaki, Kazuhiko Terada, Tomohiro Morita, Shin‐ya Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title | Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title_full | Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title_fullStr | Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title_full_unstemmed | Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title_short | Urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
title_sort | urine volume to hydration volume ratio is associated with pharmacokinetics of high‐dose methotrexate in patients with primary central nervous system lymphoma |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525095/ https://www.ncbi.nlm.nih.gov/pubmed/34664791 http://dx.doi.org/10.1002/prp2.883 |
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