A 1-year pharmacokinetic investigation of a novel oral contraceptive containing drospirenone in healthy female volunteers.
Drospirenone is a novel synthetic progestogen with a pharmacological profile similar to that of natural progesterone. It has been developed in combination with ethinylestradiol for use as an oral contraceptive (EE/DRSP, Yasmin, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of drospirenone and ethinylestradiol have been assessed in healthy female volunteers over a 1-year period. During each of the 13 treatment cycles, volunteers received the combined active ingredients for 21 days, followed by a 7-day, tablet-free interval. The concentrations of the serum proteins, sex hormone binding globulin (SHBG) and corticoid binding globulin (CBG), were determined at intervals after the cessation of treatment (day 21) at the end of cycles 1, 6, 9 and 13. Drospirenone and ethinylestradiol were found to be absorbed rapidly and to reach a peak concentration in serum 1.5-2.0 h after dosing. Serum concentrations ofdrospirenone declined, with mean terminal half-lives of 30.8-32.5 h. Accumulation of both drospirenone and ethinylestradiol was observed within a treatment cycle, with a mean accumulation ratio of 3.0 for drospirenone and 2.1 for ethinylestradiol. In addition, serum drospirenone concentrations increased between treatment cycles 1 and 6, but remained steady thereafter, as reflected in the AUC values determined at the end of treatment cycles 1, 6, 9 and 13. Serum SHBG and CBG concentrations declined in a biphasic manner after cessation of treatment at the end of cycle 13, and physiological steady-state concentrations were reached within 4-6 weeks. In conclusion, drospirenone was absorbed at a similar rate as other synthetic progestogens contained in various oral contraceptives, as indicated by similar tmax values. The terminal half-life of drospirenone was intermediate between those of 19-nortestosterone derivatives like desogestrel, levonorgestrel or gestodene and C21-progestogens like cyproterone acetate. Both active ingredients of the new contraceptive EE/DRSP showed accumulation within a treatment cycle, which is also the case with other synthetic progestogen/ethinylestradiol combinations. Similar to other oral contraceptives, a reversible induction of serum SHBG and CBG concentrations was observed under EE/DRSP treatment.
Blode
H
H
Clinical Pharmacokinetics, Metabolism and Bioanalysis, Schering AG, Berlin, Germany.
Wuttke
W
W
Loock
W
W
Röll
G
G
Heithecker
R
R
D000328:Adult; D000736:Androstenes / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002352:Carrier Proteins / Q000097:blood; D003280:Contraceptives, Oral, Synthetic / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D045167:Progesterone Congeners / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*
D000736:Androstenes; D002352:Carrier Proteins; D003280:Contraceptives, Oral, Synthetic; D045167:Progesterone Congeners; D012738:Sex Hormone-Binding Globulin; C035144:drospirenone