TY - JOUR
T1 - A retrospective study of the relationship between methotrexate clearance and hyperuricemia following high-dose methotrexate therapy
AU - Shibayama, Yoshihiko
AU - Yoshikawa, Yoshimi
AU - Matsumoto, Kazuaki
AU - Shimodozono, Yoshihiro
AU - Miyagoe, Taeko
AU - Kurita, Miho
AU - Kusadome, Chie
AU - Yamaguchi, Mariko
AU - Nishi, Yaeno
AU - Motoya, Toshiro
AU - Takeda, Yasuo
AU - Yamada, Kastushi
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Hyperuricemia
KW - Methotrexate
KW - Therapeutic drug monitoring
KW - Uric acid
UR - http://www.scopus.com/inward/record.url?scp=77958077231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958077231&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:77958077231
SN - 1029-2659
VL - 6
SP - 3
EP - 6
JO - Journal of Applied Therapeutic Research
JF - Journal of Applied Therapeutic Research
IS - 1
ER -