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Renal Clearance of Ascorbic Acid at Different Dose Levels
註釋The renal clearance of vitamin C administered orally was evaluated in human beings. New analytical methods were used for the measurement of plasma and urine concentrations utilizing high performance liquid chromatograhy with electrochemical detection. The accumulation of ascorbic acid in urine has been measured. The absorption of orally administered vitamin C appears to be saturable. The experimental design was a complete three-way crossover in four healthy subjects who had pre-study fasting vitamin C plasma concentrations above 8 ug/ml. Tweleve-hour blood and urine sample profiles were measured on days 7, 14, and 28 after dosing vitamin C 500 mg. 1000mg and 2000 mg for one week respectively. The dietary intake of high vitamin C foods and meal time remained constant for the entire study. The assayed plasma concentrations for ascorbic acid rose to maximum concentrations of 23.2 ± 6.7, 24.2 ±6.0 and 26.9 ± 8.3 ug/ml at about 3 hours for oral doses 500 mg, 1000 mg and 2000 mg. Mean AUCs calculated by the trapezoid method to the last data point were 206.0 ± 50.5, 212.1± 40.7 and 231.8 }171} 52.6 ug x hr/ml for 500 mg. 1000 mg and 2000 mg respectively. It was found that from 37.5% to 89.5%, 19.6% to 72.2% and 19.1% to 46.6 % of orally administered doses of 500 gm, 1000 mg and 2000 mg accumulated in urine over 12 hours. The results show that renal clearance increases as the plasma concentration increases from 12 to 32 ug/ml. Renal clearance following orally administered vitamin C was non-linear as small increases in plasma ascorbic acid concentration correlated with large increases in renal clearance. Four models of renal clearance, Cl subscript R = Cp subscript mid, Cl subscript R = Cp subscript mid x flow rate, Cl subscript R = Cp subscript mid x flow rate s pH or urine, Cl subscript r = percent recovered in urine, were assumed and tested by SAS. R-square data showed that renal clearance of vitamin C was dependent on the plasma concentration, urine flow rate and pH value of urine. In order to evaluate the true renal clearance at higher plasma concentration of vitamin C, a combination of oral and intravenous administration would be necessary.