A retrospective study of the relationship between methotrexate clearance and hyperuricemia following high-dose methotrexate therapy

Yoshihiko Shibayama, Yoshimi Yoshikawa, Kazuaki Matsumoto, Yoshihiro Shimodozono, Taeko Miyagoe, Miho Kurita, Chie Kusadome, Mariko Yamaguchi, Yaeno Nishi, Toshiro Motoya, Yasuo Takeda, Kastushi Yamada

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Abstract

Recent studies have revealed that methotrexate (MTX) is excreted by organic anion transporters (OATs), which can be inhibited by uric acid (UA). It has been reported that renal clearance of MTX was decreased in hyperuricemic rats. Here we report the relationship between MTX clearance and hyperuricema in high-dose MTX (HDMTX) chemotherapy. The authors retrospectively studied the concentration of UA in serum and the MTX clearance of 10 patients (21 cases) with HDMTX from Kagoshima University Hospital (Kagoshima, Japan). The serum UA concentration of 21 cases was significantly increased after HDMTX (pre-HDMTX: 4.11 ± 1.36 mg/dl, post-HDMTX: 5.78 ± 1.77 mg/dl, mean ± SD, p<0.0005). Abnormal values of UA (greater than 7 mg/dl) were observed in 6 cases in this study. The serum concentration of UA was transiently increased. A positive correlation between the elevation rate of serum UA and the half-life of MTX (r=0.618; p=0.002; 95%CI, 0.254 to 0.829) was observed. In conclusion, this retrospective study shows that HDMTX treatment induces hyperuricemia, suggesting that hyperuricemia may be a risk factor for delayed clearance of MTX in HDMTX chemotherapy.

Original languageEnglish
Pages (from-to)3-6
Number of pages4
JournalJournal of Applied Therapeutic Research
Volume6
Issue number1
Publication statusPublished - 2006 Dec 1

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Keywords

  • Hyperuricemia
  • Methotrexate
  • Therapeutic drug monitoring
  • Uric acid

ASJC Scopus subject areas

  • Pharmacology

Cite this

Shibayama, Y., Yoshikawa, Y., Matsumoto, K., Shimodozono, Y., Miyagoe, T., Kurita, M., Kusadome, C., Yamaguchi, M., Nishi, Y., Motoya, T., Takeda, Y., & Yamada, K. (2006). A retrospective study of the relationship between methotrexate clearance and hyperuricemia following high-dose methotrexate therapy. Journal of Applied Therapeutic Research, 6(1), 3-6.