Pharmacokinetic Study Of Intraperitoneal Chemotherapy With Mitomycin C Bound Activated Carbon Particles

Gastric cancer is a common disease in China. The death rate of gastric cancer is higher than other kinds of cancer, and more than 160,000 patients died of it every year. The five-year surviving rate of advanced gastric cancer cases is only about 20%. Intraabdominal recurrence and metastasis always occur even those cases undergoing radical gastrectomy.Peritoneal metastasis are frequently found in postoperative cases, and the reason is that gastric cancer cells implant in peritoneal cavity before and during gastrectomy. This kind of implantation is almost inevitable, especially when gastric cancer has infiltrated the serosal surface.Activated carbon (CH) particles can adsorb large quantities of mitomycin C (MMC) and will be concentrated in lymph node after administrated into peritoneal cavity as MMC-CH. Then mitomycin C absorbed by activated carbon particles will be released slowly in lymph node, which is the major route of metastasis of gastric cancer cells. The concentration of MMC maintains high even after 24 hours of administration, at the same time the MMC level in serum is low. There is a dynamic balance between free MMC and adsorbed MMC. The relation can be described with a formula: Q =77C026 in N.S., 37癈 (Q = adsorbed MMC (ug/mg), C = free MMC (jig/mg)). The fact is that when the level of free MMC decreases, the adsorbed MMC will be released from activated carbon particles. Then the concentration of MMC will be maintained stably for a long time.An animal experiment on nude mice with the model of human gastric cancer was completed to distinguish the different pharmacokinetic characteristics betweenMMC-CH, MMC solution and MMC-IV used in intraperitoneal chemotherapy (IPC) by high performance liquid chromatography (HPLC), and the pharmacokinetic parameters of MMC concentration were analyzed by using a computer program of SPSS. The results are as follow:1. The MMC concentration of MMC-CH group is significantly higher than MMC group and MMC-IV group in peritoneal exudate, omentum and lymph node. On the contrary, the MMC level in serum is significantly lower than the control groups( p < 0.05).2. The MMC concentration of MMC-IV group (control group 2 ) is significantly lower than MMC-CH group in peritoneal exudate, omentum and lymph node, but higher in serum( p < 0.05).3. The duration of higher MMC level in MMC-CH group is significantly longer than that of control groups( p < 0.05).Compared with MMC solution and MMC-IV methods, MMC-CH can provide higher MMC concentration in peritoneal tissue such as peritoneal exudate, omentum and lymph node. Furthermore, the very low MMC level in serum also reducer the toxicity of IPC. More over, the higher MMC level can maintain longer than 24 hours, and it makes MMC-CH method more remarkable. In brief, we proved that MMC-CH IPC is a efficient method to be used in gastric cancer therapy.