TY - JOUR
T1 - Cell-cycle-dependent pharmacology of methotrexate in HL-60
AU - Yamauchi, Atsushi
AU - Ichimiya, Takanobu
AU - Inoue, Kouichi
AU - Taguchi, Yukie
AU - Matsunaga, Naoya
AU - Koyanagi, Satoru
AU - Fukagawa, Tatsuo
AU - Aramaki, Hironori
AU - Higuchi, Shun
AU - Ohdo, Shigehiro
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - The role of the susceptibility of cells and the pharmacokinetics of MTX on the time-dependent change of methotrexate (MTX) pharmacologic action in HL-60 (human leukemia cell) was investigated from the viewpoints of the rhythm of DNA synthesis. The highest activity of MTX was observed at the time when DNA synthesis, dihydrofolate reductase (DHFR) activity, DHFR content, and DHFR mRNA content increased and the lowest activity was observed at the time when they decreased. There were significant time-dependent changes in MTX efflux. The result corresponded to the rhythm in MTX activity. The present study suggests that the time-dependent change of MTX activity is caused by a change in the sensitivity of cells and the pharmacokinetics of the drug. Therefore, the choice of dosing time associated with cell rhythmicity may help to achieve rational chronotherapeutics, increasing therapeutic effects.
AB - The role of the susceptibility of cells and the pharmacokinetics of MTX on the time-dependent change of methotrexate (MTX) pharmacologic action in HL-60 (human leukemia cell) was investigated from the viewpoints of the rhythm of DNA synthesis. The highest activity of MTX was observed at the time when DNA synthesis, dihydrofolate reductase (DHFR) activity, DHFR content, and DHFR mRNA content increased and the lowest activity was observed at the time when they decreased. There were significant time-dependent changes in MTX efflux. The result corresponded to the rhythm in MTX activity. The present study suggests that the time-dependent change of MTX activity is caused by a change in the sensitivity of cells and the pharmacokinetics of the drug. Therefore, the choice of dosing time associated with cell rhythmicity may help to achieve rational chronotherapeutics, increasing therapeutic effects.
UR - http://www.scopus.com/inward/record.url?scp=29144447942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29144447942&partnerID=8YFLogxK
U2 - 10.1254/jphs.FP0050761
DO - 10.1254/jphs.FP0050761
M3 - Article
C2 - 16327215
AN - SCOPUS:29144447942
SN - 1347-8613
VL - 99
SP - 335
EP - 341
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 4
ER -