International Journal of Pharmaceutics, 31 (1986) 83-89 Elsevier 83 IJP 01031 Dose-dependent absorption and excretion of vitamin C in humans Srikumaran Melethil, William D. Mason and Chian-Jo Chang Schools of Pharmacy and Medicine, Universiiy of Missouri at Kansas Ciiy, Kansas City, MO 64108-2792 (U.S.A.) (Received December 27th, 1984) (Modified version received July 30th, 1985) (Accepted January 16th, 1986) Key words: vitamin C - ascorbic acid - absorption - excretion - bioavailability zyxwvutsrqponmlkjihgfed Summary Four subjects ingested 500, 1000 and 2 000 mg of ascorbic acid daily for one week according to a three-way crossover design. Following the last dose, serial urine and plasma samples were obtained over a 12-h period. The ascorbic acid content of these samples were determined by an HPLC method employing electrochemical detection. The plasma concentration-time profiles are similar at all 3 doses, with the area under the curve values (mean f S.D.) being 206.0 f 50.5, 212.1 f 40.7, and 231.8 + 52.6 mg . h/l for the 500, 1000 and 2000 mg doses. The corresponding percents (mean + SD.) of dose recovered in urine are 73.2 f 25.7, 46.9 f 21.7 and 35.8 + 12.4. This decrease in recovery is significantly different (P < 0.05) between the 500 mg dose and the two higher doses. Renal clearance increases in proportion to plasma ascorbic acid in the concentration range (lo-40 mg/l) encountered in the study. Results from this study indicate that both gastrointestinal absorption and renal tubular reabsorption of vitamin C are saturable processes. Therefore, (1) the validity of previous studies which have used linear pharmacokinetic analyses and (2) the systemic effects to be derived from megadoses of the vitamin administered orally are open to question. Introduction For humans, vitamin C is an essential nutrient which must be supplied from exogenous sources. The pharmacokinetics of the vitamin appear to be quite complicated. As early as 1938, it was shown that a sigmoidal relationship exists between urinary clearance of ascorbic acid and its plasma con- centration in humans (Ralli et al., 1938; Friedman et al., 1940). This indicates the renal reabsorptive Correspondence: S. Melethil, Schools of Pharmacy and Medi- cine, University of Missouri at Kansas City, 2411 Holmes Street, Kansas City, MO 64108-2792, U.S.A. process is saturable. More recent evidence shows gastrointestinal absorption of the vitamin may also be saturable in man (Mayersohn, 1972). These two aspects, dealing with absorption and excretion of the vitamin, raise the possibility that increasing the oral dose of the vitamin may not pro- portionately increase its plasma concentration. Since this aspect had not been studied in the past, the objectives of this study were: (1) to examine steady-state plasma concentration of the vitamin following daily doses of 500,lOOO and 2 000 mg in humans, and (2) to re-investigate the relationship between plasma ascorbate and its renal clearance using a specific analytical method (Mason et al., 1980) for the determination of vitamin C in plasma and urine. 0378-5173/86/$03.50 0 1986 Elsevier Science Publishers B.V. (Biomedical Division)