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