Pharmacokinetics of oral contraceptive steroids after morning or evening administration.

ABSTRACT

An oral contraceptive containing ethynyloestradiol and norethisterone was administered to six women in the morning and in the evening using a cross-over design. Serum levels of ethynyloestradiol and norethisterone were measured at various times after administration. There was no significant difference in a number of pharmacokinetic parameters between the two times of administration, suggesting that morning or evening administration of the contraceptive are equally effective.

ABSTRACT

PIP An attempt was made to determine whether there were any major differences in the pharmacokinetics of the estrogen and gestagen components of a combined oral contraceptive (OC) after administration either at night or in the morning. 6 healthy volunteer females between 20-40 years of age with regular menstrual cycles were divided into 2 groups, each composed of 3 subjects. Group 1 was administered a single tablet of a combined OC at 0600 hours on day 5 or day 6 of the menstrual cycle. Group 2 was given a single tablet of the same OC at 1800 hours. 2 weeks later, Group 1 received a single tablet of the OC at 1800 hours; Group 2 was administered the OC at 0600 hours. At each study time a blood sample (10 ml) was taken from an antecubital vein prior to taking the tablet and at 0.5, 1, 2, 4, 12, and 24 hours after administration of the tablet. The blood was allowed to clot at room temperature and then centrifuged to obtain serum which was stored at -20 degrees Centigrade until analyzed. The concentrations of norethisterone and ethinylestradiol were estimated in each sample by radioimmunoassay. The OC used contained 1 mg norethisterone (NET) and 50 mcg ethinylestradiol (EE). A paired t test was used to test statistical significance between the 2 times of administration. There was no significant difference between the serum EE concentrations in the morning and evening samples taken at 2, 4, 12, and 24 hours after pill administration. For the samples taken at 0-5 and 1 hour, the concentrations in the morning samples were significantly higher than those in the evening samples. The significant differences appear to be due to a more rapid absorption of EE when the OC was given in the morning compared to the evening. In all 6 subjects the peak serum concentration was attained in less than 2 hours after morning administration of the OC. In only 3 of the 6 subjects was the peak serum concentration attained in less than 2 hours after evening administration. There were no significant differences between morning and evening administration of the OC for any of the pharmacokinetic parameters of EE. There was no significant difference between the serum NET concentrations in the morning and evening specimens at any time after OC administration. In regard to pharmacokinetic parameters for norethisterone, there were no significant differences between any of these values for morning or evening administration of OC. The study findings suggest that morning or evening administration of the OC was equally effective.