Estimation of the 5-methyltetrahydrofolate apparent volume of distribution in humans.
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.
Institute of Food Research, Norwich Research Park, Norwich, UK.
Maria J
MJ
King
Eid I
EI
Brima
Jack R
JR
Dainty
David A
DA
Barrett
Anthony J
AJ
Wright
Gavin
G
Willis
Paul M
PM
Finglas
D000328:Adult; D001682:Biological Availability; D002247:Carbon Isotopes; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013763:Tetrahydrofolates / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002247:Carbon Isotopes; D013763:Tetrahydrofolates; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate