Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion.
OBJECTIVE
To develop a new pharmacokinetic model for ascorbic acid (vitamin C) since no previously published model describes ascorbic acid absorption and disposition over a broad physiologic range of doses and plasma concentrations.


METHODS
A new model was developed through exploratory simulations. The model was fitted to pharmacokinetic data obtained from seven healthy volunteers who underwent ascorbic acid depletion then gradual repletion. Concentrations of ascorbic acid were measured in plasma and urine. Final pharmacokinetic model parameter estimates were obtained using nonlinear regression analysis.


RESULTS
The new model included saturable absorption, distribution and renal tubular reabsorption parameters. The model described ascorbic acid concentrations in plasma, cells, and urine during depletion and gradual repletion phases with a residual error less than 15%.


CONCLUSIONS
The model was useful for obtaining a new understanding of the likely causes for the complex concentration-time profile observed during gradual repletion. At doses of 200 to 2500 mg per day, the plateau in pre-dose concentrations is largely due to apparent saturation of tissue uptake and less a function of oral bioavailability and renal excretion than previously thought.
Graumlich
J F
JF
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria 61656-1649, USA. JFG@uic.edu
Ludden
T M
TM
Conry-Cantilena
C
C
Cantilena
L R
LR
Wang
Y
Y
Levine
M
M
D000328:Adult; D001205:Ascorbic Acid / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D008297:Male; D008954:Models, Biological; D011446:Prospective Studies
D001205:Ascorbic Acid