Early Recognition of Patients with Decreased Methotrexate Clearance Following High-Dose Methotrexate Infusion Therapy

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タイトル ( eng )
Early Recognition of Patients with Decreased Methotrexate Clearance Following High-Dose Methotrexate Infusion Therapy
作成者
Ikeda Hiroaki
Kuwata Naoharu
Arai Shigeaki
Miyake Katsushi
Kitaura Teruaki
Fujimura Kingo
Kuramoto Atsushi
Fukuchi Hiroshi
収録物名
Hiroshima Journal of Medical Sciences
45
2
開始ページ 57
終了ページ 62
収録物識別子
[PISSN] 0018-2052
[EISSN] 2433-7668
[NCID] AA00664312
抄録
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.
著者キーワード
High-dose methotrexate infusion
Decreased clearance
Criterion
Drug monitoring
Renal function
NDC分類
医学 [ 490 ]
言語
英語
資源タイプ 紀要論文
出版者
Hiroshima University Medical Press
発行日 1996-06
出版タイプ Version of Record(出版社版。早期公開を含む)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0018-2052
[NCID] AA00664312