Bioavailability of levonorgestrel from intravaginal rings in women of low income groups
Madhavan Nair, K.; Sivakumar, B.; Prema, K.; Narasinga Rao, B.S.
Contraception 33(3): 307-322
1986
ISSN/ISBN: 0010-7824 PMID: 3087697 DOI: 10.1016/0010-7824(86)90022-3Document Number: 345924
Two types of intravaginal rings (IVR) containing 50-128 mg of levonorgestrel (LNOG) and 28-60 mg of estradiol were inserted in 18 apparently normal subjects belonging to the low socioeconomic group on day 5 of the cycle. A total of 120 cycles were studied with cyclic insertion and withdrawal. Data on menstrual cycle changes were noted. For bioavailability study, blood samples were collected twice weekly for a period of one month in the first cycle in 8 women. All the plasma samples were analysed for LNOG and progesterone by RIA. Cycle control was excellent in IVR users. Expulsion of the ring was noted in 4 instances. The plasma LNOG levels were found to reach a peak level ranging from 2.7-7.5 ng/ml within 4 days after the IVR insertion. In between day 9 to 24, the plasma levels appeared to be almost steady, and once the ring was removed, the levels dropped off rapidly. The mean plasma LNOG calculated during the steady-state period of the cycle ranged from 1.6-5.1 ng/ml. These mean LNOG levels were found to be inversely correlated with skin-fold at triceps. In all the subjects ovulation was found to be inhibited, as reflected by plasma progesterone values. The range of release rates calculated from plasma steady-state values was 51-119 .mu.g/day. The average release rates over the entire period of observation based on area under curve were 102-200 .mu.g/day. On the other hand, the release rates obtained from the residual drug in the ring after a period of use ranged from 184-259 .mu.g/day.