Objective: To verify if and to which extent the interaction with grapefruit juice can increase bioavailability of orally administered sexual steroids. Design: Pilot pharmacokinetics study. Setting: Department of Obstetrics and Gynecology and Institute of Pharmacology, Medical Faculty, Palacký University, Olomouc; Department of Nuclear Medicine, University Hospital, Olomouc. Methods: 2 mg of estradiol valerate and 100 mg of micronized progesterone were given to eight healthy postmenopausal volunteers. Blood samples were collected at time 0, 2, 3, 5 and 24 hours after tablets application. The same trial was repeated a week later but tablets were swallowed with 200 ml of grapefruit juice. Serum levels of estradiol and progesterone were measured by RIA. Results were statistically evaluated using the Wilcoxon’s nonparametric paired test. Results: Though grapefruit juice on average slightly increased serum levels of estradiol (E2) and progesterone, this increase reached statistical significance only for the E2 level 24 hours after application of tablets. The mean area under curve (AUC) of estradiol rose significantly to 117%. The even greater increase in the mean AUC of progesterone (to 125 %) was not statistically significant because of marked individual variability of response. Conclusions: Our results suggest that grapefruit juice may increase bioavailability of orally administered estradiol and progesterone. The response varies markedly between individuals. This observation may be of some importance also for users of OC and HRT.

        Key words: grapefruit juice interaction, CYP3A4, bioavailability, estradiol valerate, micronized progesterone, oral application