Short-term biological variation of plasma uracil in a Caucasian healthy population.

Abstract

Plasma uracil is a new biomarker to assess theactivity of dihydropyrimidine dehydrogenase before cancer treatment with fluoropyrimidine drugs. Knowledge on the biological variation of plasma uracil is important toassess the applicability of plasma uracil as a biomarker of drug tolerance and efficacy. A total of 33 apparently healthy individuals were submitted to sequential blood draws for three days. On thesecond day, blood draws were performed every third hour for 12h. Plasma uracil was quantified by LC-MS/MS. The within-subject (CVI) and between-subject (CVG) biological variation estimates were calculated using linear mixed-effects models. The overall median value of plasma uracil was 10.6ng/mL (range 5.6-23.1ng/mL). The CVI and CVG were 13.5 and 22.1%, respectively. Plasma uracil remained stable during the day, and there was no day-to-day variation observed. No differences in biological variation components were found between sex and no correlation to age was found. Four samples were calculated to be required toestimate the homeostatic set-point ±15% with 95% confidence. Plasma uracil is subject to tight homeostatic regulation without semidiurnal and day-to-day variation, however between-subject variation exists. This emphasizes plasma uracil as a well-suited biomarker for evaluation ofdihydropyrimidine dehydrogenase activity, but four samples are required to establish the homeostatic set-point in a patient.