Intratumoural injection of calcium channel blocker enhances cytotoxicity of adriamycin in Ehrlich ascites solid tumour.
We found that the concentration of adriamycin (ADM) within the tumours were nicardipine hydrochloride (Nic) dose-dependent reaching a maximum at a Nic dose of 33.3 mg/kg body weight when Nic was injected intratumourally. In a time-course study, the maximum level of ADM after intratumoural injection of Nic was 1.3-fold higher than the maximum level with both intraperitoneal (ip) injection of Nic and ADM, but occurred later, i.e. 5 h vs 2 h respectively following exposure. Intratumoural injection of Nic prolonged the retention of ADM within the tumour, resulting in concentration levels greater than 0.5 micrograms/g of tumour, 5 to 9 h after exposure. Intraperitoneal injection of Nic and ADM and ip ADM alone resulted in peak intratumoural levels after 2 h that quickly fell after the third hour of exposure to below 0.3 micrograms/g of tumour. Furthermore, in experiments aimed at investigating the therapeutic efficacy of ADM with intratumoural vs ip injection of Nic, we found a 2.8-fold increase in the tumouricidal activity of ADM, when Nic was concurrently injected within the tumour than when it was given intraperitoneally. We conclude that intratumoural injection of Nic enhanced not only acquisition and retention of ADM by Ehrlich ascites tumour tissue, but also strengthened its tumouricidal potency.
Matsuoka
H
H
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sugimachi
K
K
Kuwano
H
H
Yano
K
K
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D007267:Injections; D007274:Injections, Intraperitoneal; D051379:Mice; D009529:Nicardipine / Q000494:pharmacology*; D014018:Tissue Distribution
D004317:Doxorubicin; D009529:Nicardipine