Electrical Stimulation Prolongs the Survival Days of Leukemic Mice Treated With Methotrexate.

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  • Uemura Naoto
    Department of Clinical Pharmacology and Therapeutics, Oita Medical University
  • Nakamura Koichi
    Department of Clinical Pharmacology and Therapeutics, Oita Medical University
  • Ishii Yoko
    Department of Ophthalmology, Oita Medical University
  • Matsukubo Seiichiro
    Department of Clinical Pharmacology and Therapeutics, Oita Medical University
  • Nyu Seiji
    Department of Clinical Pharmacology and Therapeutics, Oita Medical University
  • Nakano Shigeyuki
    Department of Clinical Pharmacology and Therapeutics, Oita Medical University

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Abstract

To investigate effects of electrical stimulation on survival days of leukemic mice treated with methotrexate (MTX), L1210-bearing mice were treated by MTX and calcium folinate (leucovorin®) rescue therapy (MTX: 400 mg/kg, followed by leucovorin at the dose of 7.5 mg/kg at 8, 15 and 24 hr after MTX) under electrical stimulation (foot shock: shock amplitude, 0.4 mA; voltage, 60 - 100 V/cm; shock duration, 5 sec; frequency, 0.5 Hz) of various lengths. The survival days were significantly prolonged by 6-hr electrical stimulation in combination with MTX, while plasma MTX concentrations and pharmacokinetic parameters such as the area under the curve (AUC0 - 12 hr) and clearance (CL) were not significantly altered. Psychological stress did not alter the efficacy of MTX in the communication box paradigm. Amplified efficacy of MTX was shown in a length-dependent manner when electrical stimulation of various lengths were applied to L1210-bearing mice.

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