Aim With comparison of pharmacokinetic profiles of levonorgestrel after single and multiple administration of the combined
oral
contraceptive, this study would provide pharmacokinetic data for safety evaluation on proloned treatment of this monthly long_acting oral contraceptive. Methods Nine healthy fertile women received the monthly
combined oral contraceptive (containing LNG 6 mg and quinestrol 3 mg) for up to 1 year. Blood samples were collected immediately prior to drug intake and at consecutive time points after oral administration for determination of serum LNG by RIA. Intraindividual comparison was applied in this longitudinal study. Results Serum LNG concentration_time curve showed an open two compartment model after single dose administration, with 2.86±1.60 hours for αT1/2 and 1.52±0.35 days for βT1/2. C max of LNG was observed after 2.56±1.13 h in the 1st treatment cycle. Mean Cmax was 141.36±70.20 nmol/L with significant interindividual variation. C max in 12 th treatment cycle reached to 314.83±128.55 nmol/L,which was much higher than that in the 1st cycle. AUC 0～28 were 182.42±135.85 and 533.96±319.31 nmol/L·d-1,respectively, also showing statistically significant difference. There was no meaningful difference on T max after single and multiple dosing. The mean value of βT1/2 in the 12th dosing was 1.67±0.48 days, which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Cd21 declined below 100 pg/ml. Conclusion There was no obvious accumulation of LNG after repeated dosing of this monthly long_acting combined oral contraceptive.