5-fluorouridine-5--triphosphate and Hand-Foot-Syndrome

Capecitabine is an oral pro-drug of 5-fluorouracil. Patients with solid tumours who are treated with capecitabine may develop hand-and-foot syndrome (HFS) as side effect. This might be a result of accumulation of intracellular metabolites. We characterised the pharmacokinetics (PK) of 5-fluorouridine 5'-triphosphate (FUTP) in peripheral blood mononuclear cells (PBMCs) and assessed the relationship between exposure to capecitabine or its metabolites and the development of HFS. Plasma and intracellular capecitabine PK data and ordered categorical HFS data was available. A previously developed model describing the PK of capecitabine and metabolites was extended to describe the intracellular FUTP concentrations. Subsequently, a continuous-time Markov model was developed to describe the development of HFS during treatment with capecitabine. The influences of capecitabine and metabolite concentrations on the development of HFS were evaluated. The PK of intracellular FUTP was described by an one-compartment model with first-order elimination (k

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Biological Variation, Population; Capecitabine; Computer Simulation; Datasets as Topic; Dose-Response Relationship, Drug; Drug Dosage Calculations; Hand-Foot Syndrome; Humans; Leukocytes, Mononuclear; Markov Chains; Models, Biological; Neoplasms; Primary Cell Culture; Prodrugs; Uridine Triphosphate