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ID 37841
file
creator
Ikeda, Hiroaki
Kuwata, Naoharu
Arai, Shigeaki
Miyake, Katsushi
Kitaura, Teruaki
Fujimura, Kingo
Kuramoto, Atsushi
Fukuchi, Hiroshi
subject
High-dose methotrexate infusion
Decreased clearance
Criterion
Drug monitoring
Renal function
NDC
Medical sciences
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.
journal title
Hiroshima Journal of Medical Sciences
volume
Volume 45
issue
Issue 2
start page
57
end page
62
date of issued
1996-06
publisher
Hiroshima University Medical Press
issn
0018-2052
ncid
language
eng
nii type
Departmental Bulletin Paper
HU type
Departmental Bulletin Papers
DCMI type
text
format
application/pdf
text version
publisher
department
University Medical Hospital
Research Institute for Radiation Biology and Medicine
Graduate School of Biomedical Science
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