ABSENCE OF AN EFFECT OF HIGH VITAMIN-C DOSAGE ON THE SYSTEMIC AVAILABILITY OF ETHINYL ESTRADIOL IN WOMEN USING A COMBINATION ORAL-CONTRACEPTIVE

Previous studies in small numbers of women have suggested that the adm inistration of gram quantities of ascorbic acid interferes with the co nversion of ethinyl estradiol (EE(2)) to its sulfates, leading to high er blood levels of EE(2). The possibility of such potentiation has bee n investigated in 37 women using a combination monophasic oral contrac eptive (30 mu g EE(2) and 150 mu g levonorgestrel) for two consecutive cycles. Concomitant daily administration of 1 g ascorbic acid taken 1 /2 hour before OC intake, was randomly assigned to the first or second cycle of OC use. On the first and 15th day of OC intake, blood sample s were drawn 11 times over a 12-hour interval and C-max and AUC(0-12 h ) calculated. On pill days 10 and 21, only 6-hour post-intake samples were obtained. Samples were analyzed for levels of ascorbic acid, free and sulfated ethinyl estradiol (and a number of other parameters). C- max and AUC values for EE(2) and EE(2)-sulfate in cycles with and with out ascorbic acid were evaluated statistically by the Grizzle model fo r days 1 and 15 and the ratios of day 15/day 1 for each of the substan ces. No effect of ascorbic acid was observed (alpha = 0.05, 1-beta = 0 .9). Only on day 15 was there a significantly lower AUC for EE(2)-sulf ate in the presence of ascorbic acid intake. Thus, the competition bet ween ascorbic acid and EE(2) for sulfation does not lead to an increas ed systemic availability of EE(2) and is, therefore, unlikely to be of any clinical importance. Ascorbic acid can, therefore, be removed fro m the list of drugs interfering with the pharmacokinetics of ethinyl e stradiol.