{'fraction_non_alphanumeric': 0.03765127745405648, 'fraction_numerical': 0.03585835948005379, 'mean_word_length': 4.35251798561151, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 3, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Early recognition of patients with decreased methotrexate clearance following high-dose methotrexate infusion therapy.

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 approximately 83 years) received a HD-MTX infusion (dosage: 1.9 approximately 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 microM). 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 microM at 6 h, 72 microM at 12 h, and 16 microM at 24 h in the low-clearance group, and those in the high-clearance group were 210 microM, 18 microM, and 1.0 microM, respectively. The estimated elimination half-lives (t1/2) at 6 approximately 12 h and 12 approximately 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 microM at 6 h and > 32 microM 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, Scr 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.