A mathematical model of the kinetics of 5-fluorouracil and its metabolites in cancer patients.

摘要: A compartmental model of the kinetics 5-fluorouracil (5-FU) and its catabolites in humans is proposed. This was developed using data from a previous study which plasma levels urinary amounts unchanged drug metabolites were quantitated after i.v. bolus injection 500 mg/m2 5-FU ten patients. Biliary excretion also quantified two subjects. The different processes, biochemical transformations, biliary adequately described by first-order kinetics. technique multiresponse modelling used for global fitting all each patient. Satisfactory agreement achieved between measured predicted values. enabled accurate avaluation pharmacokinetic parameters that could not be calculated model-free analysis. total clearance elimination half-life are reported estimated mean 6.9±3.9 min 225±352, 7.6±4, 9.6±7.7 min, respectively, three dihydrofluorouracil (FUH2), α-fluoro-β-ureidopropionic acid (FUPA), α-fluoro-β-alanine (FBAL). percentage anabolic, catabolic, urinary, quantitated. Anabolic accounted 39%±14% clearance, with substantial variation occurring among Urinary represented 6.5%±3.2%, 0.8%±0.9%, 13.2%±4.7%, 98.2%±2.5% 5-FU, FUH2, FUPA, FBAL, respectively. satisfactorily fitted to patient deficient dihydropyrimidine dehydrogenase, an enzyme previously thought rate-limiting step catabolism. In this case, catabolism highly reduced increased up 64% clearance. first patients given infusion represents further toward detailed comprehensive modeling drug.