Abstract: Aim With comparison of pharmacokinetic profiles of levonor gestrel after single and mul tiple administration of thecombined 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 themonthly combined oral contraceptive (containing LNG 6 mg and quinestrol 3 mg) for up to 1 year.Blood samples werecollectedimmediately prior to drug intake and at consecutive timepoints after oral administration for determination of serum LNG by RIA.Intraindividual comparison was appliedin this long itudinal study.Results Serum LNG concentration-t imecurve showed an open two compartment model after single dose administration, with 2.86±1.60 hours for αT_1/2 and 1.52±0.35 days for βT_1/2.C_max of LNG was observed after 2.56±1.13 h in the1sttreatment cycle.Mean C_max was 141.36±70.20 nmol/L with signif icant interindividual variation.C m ax in 12 th treatment cyclereached to 314.83±128.55 nmol/L, which was much higher than that in the1st cycle. AUC_0~28 were 182.42±135.85 and 533.96±319.31 nmol/L·d^-1, respectively, also showingstatistically significant difference.There was no meaning ful di fference on T_max after sing le and mul tiple do sing.Themean value of βT_1/2 in the12th dosing was 1.67±0.48 days, which showed no ma rked changes, sugg esting that multiple do sing did no t influence thevelocity of drug metabolism.C_d21 declined below 100 pg/ml.Conclusion There was no obvious accumulation of LNG afterrepeated dosing of this monthly long-acting combined oral contreceptive.

Key words: levonorgestrel, pharmacokinetics, combined oral contraceptive