PENETRATION KINETICS OF 5-FLUOROURACIL INTO PANCREATIC FLUID IN POST-PANCREATICODUODENECTOMY PATIENTS

Our aim was to investigate the pharmacokinetic behavior of 5-fluoroura cil (5-FU) in pancreatic fluid and to evaluate its penetration charact eristics in post-pancreatoduodenectomy patients, After completing the external drainage of the pancreatic duct during pancreatoduodenectomy surgery, eight patients were administered 1.0 g 5-FU i.v. by a 5 min i nfusion after the eighth day post-surgery on average. Blood and pancre atic fluid were collected, and the 5-FU concentrations were determined by HPLC assay, Their pharmacokinetic parameters were obtained by PCNO NLIN and statistical analysis was performed. The C-max was 20.03 +/- 1 8.25 mg/l in pancreatic fluid with a T-max of 15.6 +/- 9.5 min followi ng i.v. administration and 49.69 +/- 20.75 mg/l in plasma. 5-FU in pla sma and pancreatic fluid were all in conformity with a non-linear mode l with a K-m of 1098.08 +/- 1426.57 and 11.08 +/- 6.38 mg/l, respectiv ely, The concentrations in pancreatic fluid were similar to that obser ved in plasma with an average penetration index up to 1.01 +/- 0.49. I t is suggested therefore that 5-FU is capable of penetrating from bloo d into the pancreas as evidenced by the observed pancreatic concentrat ions, [(C) 1998 Lippincott Williams & Wilkins.].