PHARMACOKINETIC MODEL OF ASCORBIC-ACID IN HEALTHY MALE-VOLUNTEERS DURING DEPLETION AND REPLETION

Purpose. To develop a new pharmacokinetic model for ascorbic acid (vit amin C) since no previously published model describes ascorbic acid ab sorption and disposition over a broad physiologic range of doses and p lasma concentrations. Methods. A new model was developed through explo ratory simulations. The model was fitted to pharmacokinetic data obtai ned from seven healthy volunteers who underwent ascorbic acid depletio n then gradual repletion. Concentrations of ascorbic acid were measure d in plasma and urine. Final pharmacokinetic model parameter estimates were obtained using nonlinear regression analysis. Results. The new m odel included saturable absorption, distribution and renal tubular rea bsorption parameters. The model described ascorbic acid concentrations in plasma, cells, and urine during depletion and gradual repletion ph ases with a residual error less than 15%. Conclusions. The model was u seful for obtaining a new understanding of the likely causes for the c omplex concentration-time profile observed during gradual repletion. A t doses of 200 to 2500 mg per day, the plateau in pre-dose concentrati ons is largely due to apparent saturation of tissue uptake and less a function of oral bioavailability and renal excretion than previously t hought.