Naoto Uemura (1), Koichi Nakamura (1), Yoko Ishii (2), Seiichiro Matsukubo
(1), Seiji Nyu (1) and Shigeyuki Nakano (1)
(1) Department of Clinical Pharmacology and Therapeutics and (2) Department
of Ophthalmology, Oita Medical University, Hasama-machi, Oita 879-5593,
Japan
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 (R))
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.
Keywords: L1210, Methotrexate, Electrochemotherapy, Stress, Communication
box