We previously reported that methotrexate (MTX) treatment downregulated expression levels of multidrug resistance protein 2 (Mrp2), organic anion transporters (Oats), Oat1 and Oat3, in rats (Shibayama et al., 2006). It is known that Mrp2, Oat1 and Oat3 each eliminate MTX from cells. Our previous study predicts that downregulation of the transporters induced by MTX treatment can delay the clearance of MTX. We have now retrospectively studied the relationship between MTX concentration in serum and the half-life of MTX in patients treated with high-dose methotrexate (HDMTX) chemotherapy. The serum concentration of MTX and the half-life of MTX (20 patients, 38 cases) following HDMTX were analyzed in the Kagoshima University Hospital (Kagoshima, Japan). A positive correlation between the MTX concentration at 48 hours after MTX administration and the half-life of MTX (r=0.696, p<0.001, 95% confidence interval: 0.484 to 0.831) was observed. Among the 38 cases, the half-life of MTX in the high concentration group (15 cases, concentration 48 hours after MTX treatment, 4.97 ± 8.71 μM, mean ± SD) showed a longer half-life of 16.4 ± 6.4 hour (mean ± SD, p=<0.0001) than in the normal concentration group (23 cases, concentration 48 hours after MTX treatment: 0.52 ± 0.53 μM; half-life: 7.6 ± 2.3 hour; mean ± SD). In conclusion, this retrospective study indicates that a high concentration of MTX in serum may extend the half-life of MTX suggesting that a high concentration of MTX at 48 hours after MTX treatment may be a risk factor for an extended half-life of MTX in patients receiving high dose methotrexate chemotherapy.
|ジャーナル||Journal of Applied Therapeutic Research|
|出版ステータス||Published - 2008 12 1|
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