Pharmacokinetic studies with a vaginal delivery system releasing levonorgestrel at a near zero order rate for one...

Vaginal rings releasing approximately 20 micrograms levonorgestrel per 24 hours were used continuously by ten women for a period of one year. Circulating plasma levels of levonorgestrel (L-NOG) were measured every second week. Steroid hormone binding globulin (SHBG) levels were measured in the first and last four blood samples drawn. A linear relationship between the logarithms of L-NOG concentrations and duration of use was found, indicating an exponential character of decrease in L-NOG levels during the study year. An average of 72% of the mean initial levels of L-NOG was found in the circulation after 6 months' and 52% after one year's use. The L-NOG levels decreased daily by 1.1 pmol/l (0.13%) on the average. The SHBG levels were not influenced by the long-term exposure to L-NOG. The initial SHBG levels were significantly correlated (r = 0.88; P less than 0.001) to the initial L-NOG levels. The rings were well tolerated. Only in two of the ten subjects did the average number of bleeding days per month increase from a pretreatment value of 4.5 days per month to 8.3 and 9.5 days per month, respectively.