No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion
Open Access
- 1 October 1992
- journal article
- Published by Springer Nature in British Journal of Cancer
- Vol. 66 (4) , 668-672
- https://doi.org/10.1038/bjc.1992.335
Abstract
One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.Keywords
This publication has 23 references indexed in Scilit:
- The model drug approach in clinical pharmacologyClinical Pharmacology & Therapeutics, 1991
- 5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancerBritish Journal of Cancer, 1989
- PLASMA PHARMACOKINETICS OF 5-FU GIVEN BY CONTINUOUS INFUSION WITH ALLOPURINOL1986
- Clinical pharmacokinetic study of 5-FU in continuous 5-day infusions for head and neck cancerCancer Chemotherapy and Pharmacology, 1986
- Treatment of squamous-cell carcinoma of the head and neck with cisplatin and 5-fluorouracil.Journal of Clinical Oncology, 1985
- CLINICAL-TRIAL OF CISPLATIN AND 5-FU INFUSION AS INITIAL TREATMENT FOR ADVANCED SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK1982
- Nonlinear pharmacokinetic models for 5-fluorouracil in man: Intravenous and intraperitoneal routesClinical Pharmacology & Therapeutics, 1980
- Comparison of liquid- and gas-liquid chromatographic assays of 5-fluorouracil in plasma.Clinical Chemistry, 1979
- A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximationJournal of Pharmacokinetics and Biopharmaceutics, 1978
- CLINICAL-PHARMACOLOGICAL EVALUATION OF HEPATIC ARTERIAL INFUSIONS OF 5-FLUORO-2'-DEOXYURIDINE AND 5-FLUOROURACIL1978