Pharmacokinetics of gestodene in 12 women who received a single oral dose of 0.075 mg gestodene and, after a wash-out phase, the same dose during one treatment cycle

Abstract

The pharmacokinetics of gestodene (GEST) was determined in 12 healthy women (age 22 to 34 years), following single dose administration of 0.075 mg GEST. The same preparation was also administered during one treatment cycle after a wash-out phase of 1 week. After single dose administration, maximum concentrations of GEST in the serum were 4.9 ± 2.5 ng/ ml. Post maximum drug levels declined biphasically with half-lives of 0.2 ± 0.2 h and 14.9 ± 6.7 h, respectively. The apparent clearance was calculated to be 0.8 ± 0.4 ml × min −1 × kg −1. The free fraction of GEST was 1.3 ± 0.3 % and the fractions bound to SHBG and albumin were 64.3 ± 10.7 % and 34.4 ± 10.4 %, respectively. The results showed that there was a gradual decrease in serum trough levels of GEST during the cycle, due to a concomitant and equally high decrease in SHBG concentrations in the serum of about 26 %. At the end of one treatment cycle, the free fraction of GEST increased to 1.8 ± 0.5 %, the SHBG-bound fraction decreased to 57.0 ± 10.2 % and the albumin-bound fraction increased to 41.3 ± 9.9 %. Total serum clearance increased during the same time period from a mean value of 0.8 to about 1.2 ml × min −1 × kg −1. The clearance of unbound GEST, however, remained unchanged. An examination of the free GEST concentrations revealed the same time course of GEST trough levels during the cycle as the simulated curve. This was derived from the pharmacokinetic parameters which were obtained after single dose administration. Thus, the present study showed that the pharmacokinetics of GEST can be fully explained on the basis of single dose pharmacokinetics and the changes in serum protein binding which were caused by a reduction of SHBG levels in the serum during chronic treatment with GEST. There was no evidence of GEST inhibiting its own metabolism.