Penetration kinetics of 5-fluorouracil into pancreatic fluid in post-pancreatoduodenectomy patients.
Our aim was to investigate the pharmacokinetic behavior of 5-fluorouracil (5-FU) in pancreatic fluid and to evaluate its penetration characteristics 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 infusion after the eighth day post-surgery on average. Blood and pancreatic fluid were collected, and the 5-FU concentrations were determined by HPLC assay. Their pharmacokinetic parameters were obtained by PCNONLIN and statistical analysis was performed. The Cmax was 20.03 +/- 18.25 mg/l in pancreatic fluid with a Tmax of 15.6 +/- 9.5 min following i.v. administration and 49.69 +/- 20.75 mg/l in plasma. 5-FU in plasma and pancreatic fluid were all in conformity with a non-linear model with a K(m) of 1098.08 +/- 1426.57 and 11.08 +/- 6.38 mg/l, respectively. The concentrations in pancreatic fluid were similar to that observed in plasma with an average penetration index up to 1.01 +/- 0.49. It is suggested therefore that 5-FU is capable of penetrating from blood into the pancreas as evidenced by the observed pancreatic concentrations.
Zhu
Z
Z
Department of Pharmacy, Peking Union Medical College (PUMC) Hospital, PUMC, Chinese Academy of Medical Sciences, Beijing, PRC.
Fu
Q
Q
Nightingale
C H
CH
Zhao
Y P
YP
Liao
Q
Q
Li
D K
DK
D001826:Body Fluids / Q000187:drug effects*; D004386:Duodenum / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*
D005472:Fluorouracil