TY - JOUR
T1 - Short-term biological variation of plasma uracil in a Caucasian healthy population
AU - Larsen, Anne Winther
AU - Madsen, Anne Tranberg
AU - Nissen, Peter H.
AU - Hoffmann-Lücke, Elke
AU - Greibe, Eva
PY - 2023/7
Y1 - 2023/7
N2 - Objectives: Plasma uracil is a new biomarker to assess the activity of dihydropyrimidine dehydrogenase before cancer treatment with fluoropyrimidine drugs. Knowledge on the biological variation of plasma uracil is important to assess the applicability of plasma uracil as a biomarker of drug tolerance and efficacy. Methods: A total of 33 apparently healthy individuals were submitted to sequential blood draws for three days. On the second day, blood draws were performed every third hour for 12 h. 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. Results: The overall median value of plasma uracil was 10.6 ng/mL (range 5.6-23.1 ng/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 to estimate the homeostatic set-point ±15% with 95% confidence. Conclusions: 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 of dihydropyrimidine dehydrogenase activity, but four samples are required to establish the homeostatic set-point in a patient.
AB - Objectives: Plasma uracil is a new biomarker to assess the activity of dihydropyrimidine dehydrogenase before cancer treatment with fluoropyrimidine drugs. Knowledge on the biological variation of plasma uracil is important to assess the applicability of plasma uracil as a biomarker of drug tolerance and efficacy. Methods: A total of 33 apparently healthy individuals were submitted to sequential blood draws for three days. On the second day, blood draws were performed every third hour for 12 h. 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. Results: The overall median value of plasma uracil was 10.6 ng/mL (range 5.6-23.1 ng/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 to estimate the homeostatic set-point ±15% with 95% confidence. Conclusions: 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 of dihydropyrimidine dehydrogenase activity, but four samples are required to establish the homeostatic set-point in a patient.
KW - 5-fluorouracil
KW - biological variation
KW - dihydropyrimidine dehydrogenase (DPD) deficiency
KW - uracil
KW - Tandem Mass Spectrometry
KW - Humans
KW - Chromatography, Liquid
KW - Biomarkers
KW - Uracil
KW - Dihydrouracil Dehydrogenase (NADP)
KW - Fluorouracil
UR - http://www.scopus.com/inward/record.url?scp=85149883661&partnerID=8YFLogxK
U2 - 10.1515/cclm-2022-1167
DO - 10.1515/cclm-2022-1167
M3 - Journal article
C2 - 36856054
SN - 1434-6621
VL - 61
SP - 1490
EP - 1496
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
IS - 8
ER -