Department of Nutrition, University of California Davis, 95616, USA.
Anal Chem. 2011 May 1;83(9):3312-8. doi: 10.1021/ac103038s. Epub 2011 Mar 31.
Radiocarbon ((14)C) is an ideal tracer for in vivo human ADME (absorption, distribution, metabolism, elimination) and PBPK (physiological-based pharmacokinetic) studies. Living plants peferentially incorporate atmospheric (14)CO(2) versus (13)CO(2) versus (12)CO(2), which result in unique signature. Furthermore, plants and the food chains they support also have unique carbon isotope signatures. Humans, at the top of the food chain, consequently acquire isotopic concentrations in the tissues and body fluids depending on their dietary habits. In preparation of ADME and PBPK studies, 12 healthy subjects were recruited. The human baseline (specific to each individual and their diet) total carbon (TC) and carbon isotope (13)C (δ(13)C) and (14)C (F(m)) were quantified in whole blood (WB), plasma, washed red blood cell (RBC), urine, and feces. TC (mg of C/100 μL) in WB, plasma, RBC, urine, and feces were 11.0, 4.37, 7.57, 0.53, and 1.90, respectively. TC in WB, RBC, and feces was higher in men over women, P < 0.05. Mean δ(13)C were ranked low to high as follows: feces < WB = plasma = RBC = urine, P < 0.0001. δ(13)C was not affected by gender. Our analytic method shifted δ(13)C by only ±1.0 ‰ ensuring our F(m) measurements were accurate and precise. Mean F(m) were ranked low to high as follows: plasma = urine < WB = RBC = feces, P < 0.05. F(m) in feces was higher for men over women, P < 0.05. Only in WB, (14)C levels (F(m)) and TC were correlated with one another (r = 0.746, P < 0.01). Considering the lag time to incorporate atmospheric (14)C into plant foods (vegetarian) and or then into animal foods (nonvegetarian), the measured F(m) of WB in our population (recruited April 2009) was 1.0468 ± 0.0022 (mean ± SD), and the F(m) of WB matched the (extrapolated) atmospheric F(m) of 1.0477 in 2008. This study is important in presenting a procedure to determine a baseline for a study group for human ADME and PBPK studies using (14)C as a tracer.
放射性碳（14C）是进行体内人体 ADME（吸收、分布、代谢、消除）和 PBPK（基于生理学的药代动力学）研究的理想示踪剂。活体植物优先吸收大气中的（14）CO2 而不是（13）CO2 和（12）CO2，这导致了独特的特征。此外，植物及其支持的食物链也具有独特的碳同位素特征。处于食物链顶端的人类，因此会根据饮食习惯在组织和体液中获得同位素浓度。在准备 ADME 和 PBPK 研究时，招募了 12 名健康受试者。在全血（WB）、血浆、洗涤红细胞（RBC）、尿液和粪便中定量测定了 12 名健康受试者的个体基线（特定于每个人及其饮食）总碳（TC）和碳同位素（13）C（δ（13）C）和（14）C（F（m））。WB、血浆、RBC、尿液和粪便中的 TC（mg C/100 μL）分别为 11.0、4.37、7.57、0.53 和 1.90。WB、RBC 和粪便中的 TC 在男性中高于女性，P < 0.05。平均 δ（13）C 从低到高排列如下：粪便 <WB=血浆=RBC=尿液，P <0.0001。性别对 δ（13）C 没有影响。我们的分析方法仅将 δ（13）C 偏移 ±1.0 ‰，从而确保我们的 F（m）测量结果准确且精确。平均 F（m）从低到高排列如下：血浆=尿液<WB=RBC=粪便，P <0.05。男性粪便中的 F（m）高于女性，P <0.05。只有在 WB 中，（14）C 水平（F（m））和 TC 彼此相关（r = 0.746，P <0.01）。考虑到将大气（14）C 纳入植物性食物（素食）和然后纳入动物性食物（非素食）的时间滞后，我们研究人群（2009 年 4 月招募）中 WB 的实测 F（m）为 1.0468 ± 0.0022（平均值±SD），并且 WB 的 F（m）与 2008 年大气中 F（m）的 1.0477 （外推）相匹配。本研究重要之处在于提出了一种使用（14）C 作为示踪剂确定人体 ADME 和 PBPK 研究中研究组基线的程序。
