Early Recognition of Patients with Decreased Methotrexate Clearance Following High-Dose Methotrexate Infusion Therapy
Use this link to cite this item : https://ir.lib.hiroshima-u.ac.jp/00037841
ID | 37841 |
file | |
creator |
Ikeda, Hiroaki
Kuwata, Naoharu
Arai, Shigeaki
Miyake, Katsushi
Kitaura, Teruaki
Fujimura, Kingo
Kuramoto, Atsushi
Fukuchi, Hiroshi
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subject | High-dose methotrexate infusion
Decreased clearance
Criterion
Drug monitoring
Renal function
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NDC |
Medical sciences
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abstract | The purpose of this study was to identify the patients with decreased methotrexate (MTX) clearance as early as possible after the start of high-dose methotrexate (HD-MTX) infusion. Fifty-six patients (age: 18~83 years) received a HD-MTX infusion (dosage: 1.9~3.8 g/m2) for 6 h. These patients were retrospectively divided into a low-clearance group and a high-clearance group based on the serum MTX concentration at 48 h (1 μM). Six out of the 56 patients showed decreased MTX clearance. The MTX concentrations in the low-clearance group were significantly higher than those in the high-clearance group even in earlier sampling times than at 48 h. The average MTX concentrations were 330 μM at 6 h, 72 μM at 12 h, and 16 μM at 24 h in the low-clearance group, and those in the high-clearance group were 210 μM, 18 μM, and 1.0 μM, respectively. The estimated elimination half-lives (t1/2) at 6~12 h and 12 ~ 24 h after the start of the infusion were also significantly longer in the low-clearance group (2.8 vs. 1.7 h and 5.0 vs. 2.8 h, respectively). Therefore, we proposed convenient criteria based on the mean + 1 S.D. of the high-clearance group: the concentration > 270 μM at 6 h and > 32 μM at 12 h; the t1/2 value > 2.1 h at 6~12 h. All 6 patients were recognized as belonging to the low-clearance group at an early stage after HD-MTX infusion by using our proposed criteria. These results indicate that patients with decreased MTX clearance could be identified within the first 12 h after the start of HD-MTX infusion. The factors influencing the prolonged elimination of MTX were also investigated. A significant decrease in renal function on day 2 was observed in the low-clearance group. The MTX level at 12 h and the estimated t1/2 values were significantly correlated with BUN, Ser and Clcr on the 2nd day after HD-MTX therapy, suggesting that an alteration in renal function occurs within 12 h of the HD-MTX infusion. The prolonged elimination of MTX could be attributable to this decrease in renal function.
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journal title |
Hiroshima Journal of Medical Sciences
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volume | Volume 45
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issue | Issue 2
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start page | 57
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end page | 62
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date of issued | 1996-06
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publisher | Hiroshima University Medical Press
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issn | 0018-2052
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ncid | |
language |
eng
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nii type |
Departmental Bulletin Paper
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HU type |
Departmental Bulletin Papers
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DCMI type | text
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format | application/pdf
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text version | publisher
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department |
University Medical Hospital
Research Institute for Radiation Biology and Medicine
Graduate School of Biomedical Science
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他の一覧 |