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Pharmacokinetics of excretory passage of 5‐fluorouracil (i.v.) into the pancreatic juice of patients with pancreatic or biliary carcinoma: Evaluation of possible adjuvant chemotherapy
Author(s) -
Takada Tadahiro
Publication year - 1995
Publication title -
journal of hepato‐biliary‐pancreatic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 0944-1166
DOI - 10.1007/bf02349261
Subject(s) - pancreatic juice , medicine , pharmacokinetics , bolus (digestion) , fluorouracil , chemotherapy , gastroenterology , pancreas , regimen , pancreatic cancer , pancreatic disease , carcinoma , urology , pharmacology , cancer
Abstract The drug, 5‐fluorouracil (5‐FU), is thought to be efficacious in treating human pancreatic or biliary carcinomas; therefore, to determine the optimal dosage for chemotherapeutic use in these conditions, we performed this pharmacokinetic study in which we investigate the passage of various doses of intravenously administered 5‐FU into the pancreatic juice of 11 patients with pancreatic or biliary carcinoma. Whenever possible, all 11 patients, who had undergone a pancreaticoduodenectomy and had an external drainage tube, received the following three regimens: (1) a bolus injection of 5‐FU, 185 mg/m 2 per day; (2) a continuous infusion of 5‐FU, 185 mg/m 2 per day over 48h (CIV‐I), and (3) a continuous infusion of 5‐FU, 370 mg/m 2 per day over 48 h (CIV‐II), with a sufficient wash‐out period of 2 weeks between each regimen. The major findings were: (i) the percentage of the administered 5‐FU dose excreted (pancreatic passage fraction; Fp) was strongly correlated with the total amount of pancreatic juice excreted over the 24‐h period (Vp) of drug testing; (ii) the Fp per 100 ml Vp (Fp′) was greater after the bolus treatment than after either CIV treatment; (iii) 90% of the 5‐FU excreted into the pancreatic juice was present within 30min of the bolus injection; and (iv), the entire body clearance (CL total ) of 5‐FU was significantly lower after the bolus injection than after either CIV treatment. It was concluded that the Fp' value was dependent on the method of 5‐FU administration, that a 5‐FU bolus injection probably inundates the hepatic metabolic capacity, and that the Fp' of 5‐FU largely depends on the patient's ability to metabolize the drug. Therefore, the efficacy of 5‐FU as an anticancer agent appears to be time‐rather than dose‐dependent.