[Pharmacokinetics following intraperitoneal sequential administration of cisplatin and fluorouracil for gastric...

Gastric cancer patients with peritoneal dissemination underwent a palliative resection of the stomach and received an intraperitoneal administration of CDDP (70 mg/m2) and 5-FU (700 mg/m2), immediately after the surgery. The levels of CDDP and 5-FU in serum and peritoneal cavity were serially monitored in order to study the pharmacokinetics of these drugs. group A (n = 9): CDDP dissolved in 500 ml saline was infused intraperitoneally at 200 ml/min, and one hour later, 5-FU dissolved in 500 ml saline was infused at the same speed. The infusion catheter was clamped for two hours after completion of 5-FU infusion. Group B (n = 3): CDDP in 500 ml saline were infused at 10 ml/min and then 5-FU in 500 ml were infused at 5 ml/min. Group C (n = 2): CDDP in 1,000 ml saline was infused at 200 ml/min. Group D (n = 2): 5-FU in 1,000 ml saline was infused at 200 ml/min. The free CDDP levels in the peritoneal cavity were 22 micrograms/ml in group A, 57 micrograms/ml in group B, and 13 micrograms/ml in group C at one hour after completion of the infusion. The 5-FU levels in the peritoneal cavity measured two hours after completion of the infusion were significantly higher in the group B (349 micrograms/ml) than in group A (132 micrograms/ml) and C (71 micrograms/ml). The Cmax of 5-FU in serum was lowest in group B. The AUCs in the peritoneal cavity of free CDDP and 5-FU were 63.6 micrograms.hr/ml and 925 micrograms.hr/ml, respectively. These values were above the 10th percentile of IC90 for gastric cancer. No serious complications were encountered in group A and B where both CDDP and 5-FU were administered as compared with group C and D, where either CDDP or 5-FU was administered.