Transfer of drospirenone to breast milk after a single oral administration of 3 mg drospirenone +30 μg ethinylestradiol to healthy lactating women

Drospirenone (DPSP) is a synthetic progestogen which has been developed in combination with ethinylestradiol (EE) for use as an oral contraceptive (Yasmin(R), Schering AG, Berlin, Germany). The pharmacokinetic characteristics ofDRSP were evaluated in serum and breast milk from lactating women who received a single oral dose of 3 mg DRSP + 30 mug EE, to determine the fraction of the dose of DRSP which transfers to breast milk. Nine healthy, lactating women were included into the present study and pharmacokinetic data were obtained from six participants. The maximum DRSP concentrations (data given as mean standard deviation) were reached on average 2.5 +/- 1.2 and 2.8 +/- 1.3 h in serum and breast milk, respectively after oral administration of 3 mg DRSP + 30 mug EE, and amounted on average to 30.8 +/- 14.4 and 13.5 +/- 11.7 ng DRSP/ml in serum and breast milk. The mean breast milk versus serum concentration ratios of DPSP increased from 0.16 to 0.57 within 2 h after dosing and decreased to 0.16 after 24 h. The average ratio of AUC(0-48 h) , values in breast milk versus serum was 0.23 +/- 0.09. The mean DRSP concentration in breast milk over the 24-h period after dosing was 3.7 +/- 1.9 ng/ml. The amount of DRSP measured to be transferred into breast milk in the six women participating in the present study was, on average, 635 ng (range 256.2-1357.9 ng) within 24 h, corresponding to about 0.02% of the maternal dose. Based on the average concentration of the drug in breast milk over 24 h and assuming a daily ingestion of approximately 800 ml breast milk, the daily dose that reaches an infant via breast milk is estimated to be approximately 3 mug DPSP. The subjective and objective tolerances of 3 mg DRSP + 30 mug EE were good, with no adverse events reported.