Electrical stimulation prolongs the survival days of leukemic mice treated with methotrexate.
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 (AUC-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.
Uemura
N
N
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Japan.
Nakamura
K
K
Ishii
Y
Y
Matsukubo
S
S
Nyu
S
S
Nakano
S
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004558:Electric Stimulation; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D013047:Specific Pathogen-Free Organisms; D013315:Stress, Psychological; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate