Newly developed drug delivery system in cancer chemotherapy using direct electric current.
To improve the antitumor effect of chemotherapy on a target organ, we experimentally investigated pharmacokinetic alteration of methotrexate (MTX) induced by an electric current in rats to ascertain whether the local concentration of MTX could be enhanced while reducing the concentration in blood. Six male Wistar rats had platinum electrodes introduced into both kidneys. Three rats were subjected to direct current (3.5 V, 50 microA) for 3 hours, while another three control rats received no current. While providing the current to the treated group, all of the rats were intravenously injected with MTX at a dose of 1 mg/kg. The MTX concentration in urine (excreted from each ureter) and serum was measured by fluorescence polarization immunoassay. Cumulative MTX renal excretion rate was significantly higher in the cathode than anode side in the treated group (p < 0.01). Serum MTX concentration at 0 to 5 min was significantly reduced in the treated group (p < 0.03). The first part of the area under the curve (i.e., alpha curve) was markedly increased in the treated group versus controls (p = 0.05). Electric therapy using a slight direct current could gather anionized MTX to the cathode, while reducing MTX concentration in the serum of experimental rats.
Ito
K
K
Department of Surgery II, Nagoya University School of Medicine, Japan.
Wong
L
L
Ando
H
H
Hibi
K
K
Hidemura
K
K
Yamazaki
T
T
Kasai
Y
Y
Akiyama
S
S
Nakao
A
A
Ikeda
S
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004599:Electric Stimulation Therapy / Q000379:methods*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate