OBJECTIVES: The purpose of this study was to examine the interpatient and intrapatient variability of the Michaelis-Menten plasma parameters of 5-fluorouracil administered according to a schedule combining a bolus of 400 mg/m2 followed by 22-hour infusion of 600 mg/m2 for 2 consecutive days. PATIENTS: A pharmacokinetic population approach was used to analyze the data from 21 patients with colorectal cancer. RESULTS: The 5-fluorouracil plasma concentrations versus time were best described by a two-compartment model with nonlinear elimination from the central compartment. The relationships between the pharmacokinetic parameters and patient characteristics were tested. On day 1 the mean values (with interindividual variability as expressed by the coefficient of variation) were 1390 mg x h(-1) (20%), and 5.57 mg x L(-1) (22%) for the maximum rate of elimination, and the half-saturating plasma concentration. The maximum rate of elimination was positively correlated to the body surface area and the percentage of liver involvement by metastatic disease determined by tomodensitometric examination. The model was successfully tested with independent data sets corresponding to other schedules. The analysis of this intrapatient variability showed that the half-saturating plasma concentration increased from day 1 to day 2, especially in the patients with low lymphocyte cell dihydropyrimidine dehydrogenase activity. CONCLUSION: The pharmacokinetic parameters obtained in this study would be useful to predict the 5-fluorouracil plasma concentrations following other schedules of administration of 5-fluorouracil and to study the possible pharmacokinetic interactions between 5-fluorouracil and other drugs.
OBJECTIVES: The purpose of this study was to examine the interpatient and intrapatient variability of the Michaelis-Menten plasma parameters of 5-fluorouracil administered according to a schedule combining a bolus of 400 mg/m2 followed by 22-hour infusion of 600 mg/m2 for 2 consecutive days. PATIENTS: A pharmacokinetic population approach was used to analyze the data from 21 patients with colorectal cancer. RESULTS: The 5-fluorouracil plasma concentrations versus time were best described by a two-compartment model with nonlinear elimination from the central compartment. The relationships between the pharmacokinetic parameters and patient characteristics were tested. On day 1 the mean values (with interindividual variability as expressed by the coefficient of variation) were 1390 mg x h(-1) (20%), and 5.57 mg x L(-1) (22%) for the maximum rate of elimination, and the half-saturating plasma concentration. The maximum rate of elimination was positively correlated to the body surface area and the percentage of liver involvement by metastatic disease determined by tomodensitometric examination. The model was successfully tested with independent data sets corresponding to other schedules. The analysis of this intrapatient variability showed that the half-saturating plasma concentration increased from day 1 to day 2, especially in the patients with low lymphocyte cell dihydropyrimidine dehydrogenase activity. CONCLUSION: The pharmacokinetic parameters obtained in this study would be useful to predict the 5-fluorouracil plasma concentrations following other schedules of administration of 5-fluorouracil and to study the possible pharmacokinetic interactions between 5-fluorouracil and other drugs.
Authors: Jan H Beumer; Edward Chu; Carmen Allegra; Yusuke Tanigawara; Gerard Milano; Robert Diasio; Tae Won Kim; Ron H Mathijssen; Li Zhang; Dirk Arnold; Katsuki Muneoka; Narikazu Boku; Markus Joerger Journal: Clin Pharmacol Ther Date: 2018-09-11 Impact factor: 6.875
Authors: André B P van Kuilenburg; Peter Häusler; Andreas Schalhorn; Michael W T Tanck; Johannes H Proost; Christoph Terborg; Detlev Behnke; Wolfgang Schwabe; Kati Jabschinsky; Jan Gerard Maring Journal: Clin Pharmacokinet Date: 2012-03-01 Impact factor: 6.447
Authors: Z Daher Abdi; S Lavau-Denes; A Prémaud; S Urien; F L Sauvage; J Martin; S Leobon; P Marquet; N Tubiana-Mathieu; A Rousseau Journal: Cancer Chemother Pharmacol Date: 2014-05-07 Impact factor: 3.333