[Pharmacokinetic study of postoperative peritoneal infusion with large bulk heated hypotonic 5-fluorouracil fluid for prevention of recurrence and hepatic metastasis of gastric cancer].
OBJECTIVE
At present, only few animal experiment has been reported about the pharmacokinetic of peritoneal chemotherapy. The aim of this study was to determine the pharmacokinetic change following large bulk heated hypotonic 5-fluorouracil fluid perfusing into peritoneal immediately after radical resection.


METHODS
(1) Fifty patients with gastric cancer after radical resection were randomly assigned into ten groups. They were given intraperitoneal infusion of warm (43 degrees C-45 degrees C) distilled water (1,250 ml/m2) plus 5-fluorouracil (500 mg/L) after radical gastrectomy. At various time intervals (0, 0.08, 0.25, 0.5, 0.75, 1, 3, 6, 12, 24 h), blood samples from the femoral artery and vein, portal vein, and peritoneal fluid were collected. (2) 25 cases of patients with gastric cancer were randomized into five groups, each group also included 5 cases. They were also given intraperitoneal infusion at 1, 3, 6, 12, 24 h with the same fluid before operation, blood samples from portal vein were drawn at the beginning of operation. (3) 5-fluorouracil concentration of above all of samples were determined by high performance liquid chromatography (HPLC).


RESULTS
(1) The peak concentration of peritoneal fluid, portal vein, femoral artery and vein were at 0, 0.08, 1.00, 1.00 h, respectively, after peritoneal infusion. (2) The peak and average concentration in peritoneal fluid were 167.7-fold and 180.4-fold as high as that of the femoral vein respectively. (3) The peak and average concentration in portal vein were 5.4-fold and 6.7-fold as high as that of the femoral vein respectively. (4) The concentration changes of 5-fruorouracil in peritoneal fluid, portal vein, femoral artery and vein were all suitable for two compartment open model. The pharmacokinetics parameters of above all the fluid were in turn: AUC0-->tn(mg.L-1.h) 3667.36, 143.82, 31.02, 26.84; alpha(h-1) 1.1076, 0.6269, 7.7923, 21.5643; beta(h-1) 0.0367, 0.0474, 0.2091, 0.2014; CL(L.h-1) 0.16, 4.92, 35.36, 39.32; T1/2 alpha(h) 0.62, 1.11, 0.09, 0.03; T1/2 beta(h) 18.88, 14.64, 3.31, 3.44; (5) The portal vein 5-fluorouracil concentration at various times were all lower than that of the preoperation, suggesting that 5-fluorouracil can pass through retroperitoneal spaces into systemic circulation.


CONCLUSIONS
Postoperative large bulk heated hypotonic fluid peritoneal infusion with 5-fluorouracil has pharmacokinetic characteristic of high selective regional chemotherapy providing higher and lasting concentration in peritoneal fluid and portal vein. Therefore, this method should be a more reasonable chemotherapy for the prevention of recurrence and liver metastasis of gastric cancer after radical resection.
Lin
Ai-de
AD
Department of General Surgery, Linyi City Tumor Hospital, Linyi 276001, P. R. China.
Sun
Huai-yu
HY
Qu
Mou-wen
MW
Wang
Fu-jiang
FJ
Wang
Jing-ying
JY
Li
Zeng-jun
ZJ
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D007263:Infusions, Parenteral; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D011182:Postoperative Care; D055502:Secondary Prevention; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil