Pharmacokinetics of mitomycin C (MMC) after intraperitoneal administration of MMC-gelatin gel and its anti-tumor effects against sarcoma-180 bearing mice.
Gelatin viscous solution containing mitomycin C (MMC) was prepared and its antitumor effects were evaluated toward sarcoma-180 (S-180) ascite tumor bearing mice. Among various gelatin concentrations, 3% and 5% gelatin solutions potentiated the antitumor effects of MMC (7.5 mg/kg) against S-180 bearing mice. A "bell-shaped" profile was observed between % release of MMC from the gelatin matrix and increased life span (ILS) %. On the other hand, in the case of 10 mg/kg dose of MMC, 7.5% and 10% gelatin solutions potentiated its antitumor effects. At both doses of 7.5 and 10 mg/kg of MMC, decrease in body weight of mice after intraperitoneal administration of MMC were suppressed by increasing the concentration of gelatin. To confirm a possible mechanism for increase in ILS % after intraperitoneal (i.p.) administration of the gelatin viscous solution containing MMC, we examined the pharmacokinetics of MMC after i.p. administration into rats. By the use of 3 % gelatin solution, mean residence time (MRT) and Tmax values were significantly prolonged, and Cmax was decreased as compared with the administration of MMC solution. These results suggested that the enhancement of antitumor effect of MMC by the gelatin viscous solution could be caused by decrease in the clearance rate of MMC from the peritoneal cavity to systemic circulation due to decreasing its diffusivity in gelatin matrix.
Fujita
T
T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Tamura
T
T
Yamada
H
H
Yamamoto
A
A
Muranishi
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D001835:Body Weight / Q000187:drug effects; D005780:Gelatin / Q000008:administration & dosage*; D005782:Gels; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012510:Sarcoma 180 / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D005782:Gels; D016685:Mitomycin; D005780:Gelatin