Modeling 5-FU clearance during a chronomodulated infusion

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.