Institute of Food Research, Norwich Research Park, Norwich, UK.
J Nutr. 2012 Feb;142(2):389-95. doi: 10.3945/jn.111.143685. Epub 2012 Jan 5.
The fractional absorption of a stable isotope-labeled folate dose can be estimated from the subsequent short-term temporal changes in the concentration of labeled L-5-methyltetrahydrofolate (L-5-methyl-THF) in plasma using mathematical modeling. However, the model is dependent on the use of an accurate value for the apparent volume of distribution of L-5-methyl-THF. Previous studies that estimated the apparent volume of distribution of L-5-methyl-THF used large (nonphysiological) doses of unlabeled folates that are not found to any great extent in the circulatory system. The current study estimates the apparent volume of distribution at steady state in 16 healthy humans aged 18-65 y after an i.v. dose (440 nmol) of a stable isotope-labeled version of the naturally circulating plasma folate, L-5-methyl-THF. Blood was collected from 2 min to 2 h postinjection and plasma assayed by specific and sensitive liquid chromatography-tandem MS. The apparent volume of distribution for L-5-methyl-THF was 32.0 ± 11.6 L (mean ± SD; 392 ± 110 mL/kg bodyweight). There was a positive association with volunteer body weight (r = 0.64; P = 0.010), which allowed a simple linear equation to be developed relating apparent volume of distribution to body weight. This has important implications for predicting apparent absorption of labeled folates in future bioavailability studies.
可以使用数学模型，根据随后的血浆中标记的 L-5-甲基四氢叶酸（L-5-甲基-THF）浓度的短期时间变化，来估算稳定同位素标记的叶酸剂量的分数吸收。但是，该模型依赖于使用 L-5-甲基-THF 的表观分布容积的准确值。先前估计 L-5-甲基-THF 的表观分布容积的研究使用了大量（非生理）的未标记叶酸剂量，这些剂量在循环系统中并没有大量存在。本研究在 16 名年龄在 18-65 岁的健康人中，在静脉注射（440nmol）稳定同位素标记的天然循环血浆叶酸 L-5-甲基-THF 后，估计了稳态时的表观分布容积。在注射后 2 分钟至 2 小时采集血液，并通过特异性和灵敏的液相色谱-串联质谱法测定血浆。L-5-甲基-THF 的表观分布容积为 32.0±11.6L（平均值±标准差；392±110mL/kg 体重）。与志愿者体重呈正相关（r=0.64；P=0.010），这允许开发一个简单的线性方程，将表观分布容积与体重相关联。这对于预测未来生物利用度研究中标记叶酸的表观吸收具有重要意义。
