A pharmacokinetic and pharmacodynamic study with a single implant containing 3-ketodesogestrel (Implanon®)

Abstract

With the objective to investigate the pharmacokinetic and pharmacodynamic profile of a single implant containing 3-ketodesogestrel (Implanon®), 15 healthy women of fertile aged between 20 and 35, with regular cycles, and not breastfeeding were recruitted. Blood sample were drawn before and after implant inserted according to schedule. Serum concentration of 3 keto-desogestrel for the first six weeks after implant insertion was 709 pg/ml and had decreased to 388 pg/ml at six months. Thereafter concentration further decreased slowly with time (fifth year mean 169 pg/ml, range 141 - 204 pg/ml, n=7). Maximum P concentrations remained below 16 nmol/1 in the whole treatment period for the majority of subjects. In four subjects maximum P concentrations exceeding 16 nmol/l the first six weeks. Reduced E2 concentrations were observed during the first 12 months. Thereafter mean concentrations were close to, and sometimes ex­ceeding, those observed before insertion. A large inter-subject and intra-subject variation was observed. During the first 11/2 year mean and median SHBG concentrations were below screening values. Thereafter, SHBG concentrations were close to the screening values. No pregnancies occured during treatment. No subjects discontinued due to bleeding irregularities or amenorrhoea. Overall reference periods (RPs), the prevalence of a amenorrhoea ranged women 0 (for 9 out of 20 reference periods) and 33.3%. No amenorrhoea occurred from RP 14 onwards. For infrequent bleeding the range was between 20.0% and 73.3%, for number of bleeding-spotting days RP ranged from 16.5 to 31.7. The mean number of bleeding-spotting episodes ranged from 1.9 to 3.7. Two post-treatment pregnancies were reported. Return offertilty, judged from return of menses or return of luteal phase progesterone levels, could be confirmed to occur within 3 months after removal of the implant in seven out of eight available subjects.