研究动态
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高加索人群血浆尿嘧啶的短期生物变异。

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

发表日期:2023 Mar 02
作者: Anne Winther-Larsen, Anne Tranberg Madsen, Peter H Nissen, Elke Hoffmann-Lücke, Eva Greibe
来源: CLINICAL CHEMISTRY AND LABORATORY MEDICINE

摘要:

血浆尿嘧啶是一种新的生物标志物,用于评估荧光嘧啶类药物治疗前脱氢尿嘧啶酶的活性。了解血浆尿嘧啶的生物学变异对于评估其作为药物耐受性和疗效生物标志物的适用性非常重要。共有33名表面健康的个体连续三天进行血液采样,第二天每隔3小时采一次血。采用LC-MS / MS法定量血浆尿嘧啶,使用线性混合效应模型计算了组内(CVI)和组间(CVG)生物变异的估计值。血浆尿嘧啶的总体中位数值为10.6 ng / mL(范围为5.6-23.1 ng / mL)。CVI和CVG分别为13.5%和22.1%。血浆尿嘧啶在一天内保持稳定,未观察到日常变异。未发现性别之间的生物变异成分差异,也没有与年龄的相关性发现。计算需要四个样本才能以95%置信度估计出稳态设定点±15%。血浆尿嘧啶受到严格的稳态调节,没有半日变异和日常变异,但是组间变异存在。这强调了血浆尿嘧啶作为评估脱氢尿嘧啶酶活性的适合的生物标志物,但需要四个样本才能在患者中建立稳态设定点。 ©2023作者,由De Gruyter,柏林/波士顿出版。
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.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.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.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.© 2023 the author(s), published by De Gruyter, Berlin/Boston.