Evaluation of folic acid supplementation by concomitant administration of ethinyl estradiol + levonorgestrel in healthy female subjects .

Abstract

Folic acid supplementation prevents 50-75% of cases of neural tube defects. This study evaluated the folic acid supplementation after oral administration of the ethinyl estradiol 0.02 mg + levonorgestrel 0.10 mg + folic acid 0.4 mg coated tablet as well as its safety and tolerability in healthy female subjects. 36 healthy female subjects received 1 coated tablet of the test product - ethinyl estradiol 0.02mg + levonorgestrel 0.10mg + folic acid 0.4mg for 21days and a placebo coated tablet containing folic acid 0.4mg only on the last 7days of the cycle, in 3 cycles. Blood samples were collected to quantify folate by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The safety was assessed by recording adverse events, monitoring of vital signs, and the evaluation of laboratory tests and ECG. The mean whole blood level of folic acid at baseline (1st day of 1st cycle) was 42.7±22.2ng/mL, while on the 28th day of the 3rd cycle it was 47.6±20.1ng/mL, with a variation of 11.32%. The subjects tolerated the clinical protocol well and reported no clinically significant adverse effects. Oral contraceptives may be a good vehicle for folate supplementation in women of reproductive age.