Carbon Isotopes Profiles of Human Whole Blood, Plasma, Red Blood Cells, Urine and Feces for Biological/Biomedical ~(14)C-Accelerator Mass Spectrometry Applications

摘要

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 ((delta)~(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 (mu)L) 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 (delta)~(13)C were ranked low to high as follows: feces < WB velence plasma velence RBC velence urine, P < 0.0001. (delta)~(13)C was not affected by gender. Our analytic method shifted (delta)~(13)C by only +-1.0(per thousand) ensuring our F_(m) measurements were accurate and precise. Mean F_(m) were ranked low to high as follows: plasma velence urine < WB velence RBC velence 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 velence 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.