Relationship between methotrexate concentration in serum and half-life of methotrexate in high-dose methotrexate therapy

A retrospective study

Yoshihiko Shibayama, Toshiro Motoya, Yoshimi Yoshikawa, Kazuaki Matsumoto, Tomohide Fukamizu, Naoko Fukunaga, Yoshihiro Shimodozono, Yasuo Takeda, Kastushi Yamada

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)25-28
Number of pages4
JournalJournal of Applied Therapeutic Research
Volume6
Issue number3
Publication statusPublished - 2008
Externally publishedYes

Fingerprint

Methotrexate
Half-Life
Retrospective Studies
Serum
Therapeutics
Down-Regulation
Organic Anion Transporters
Drug Therapy

Keywords

  • Half-life
  • Methotrexate
  • Mrp2
  • Oat
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology

Cite this

Relationship between methotrexate concentration in serum and half-life of methotrexate in high-dose methotrexate therapy : A retrospective study. / Shibayama, Yoshihiko; Motoya, Toshiro; Yoshikawa, Yoshimi; Matsumoto, Kazuaki; Fukamizu, Tomohide; Fukunaga, Naoko; Shimodozono, Yoshihiro; Takeda, Yasuo; Yamada, Kastushi.

In: Journal of Applied Therapeutic Research, Vol. 6, No. 3, 2008, p. 25-28.

Research output: Contribution to journalArticle

Shibayama, Y, Motoya, T, Yoshikawa, Y, Matsumoto, K, Fukamizu, T, Fukunaga, N, Shimodozono, Y, Takeda, Y & Yamada, K 2008, 'Relationship between methotrexate concentration in serum and half-life of methotrexate in high-dose methotrexate therapy: A retrospective study', Journal of Applied Therapeutic Research, vol. 6, no. 3, pp. 25-28.
Shibayama, Yoshihiko ; Motoya, Toshiro ; Yoshikawa, Yoshimi ; Matsumoto, Kazuaki ; Fukamizu, Tomohide ; Fukunaga, Naoko ; Shimodozono, Yoshihiro ; Takeda, Yasuo ; Yamada, Kastushi. / Relationship between methotrexate concentration in serum and half-life of methotrexate in high-dose methotrexate therapy : A retrospective study. In: Journal of Applied Therapeutic Research. 2008 ; Vol. 6, No. 3. pp. 25-28.
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abstract = "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.",
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AU - Matsumoto, Kazuaki

AU - Fukamizu, Tomohide

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AU - Shimodozono, Yoshihiro

AU - Takeda, Yasuo

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