Pharmacokinetics of Oral Combination Contraceptive Drugs Containing Ethinyl Estradiol and Levonorgestrel in Healthy Female Chinese Volunteers

Abstract

Background and Objective: A new combination contraceptive tablet containing 0.02 mg ethinyl estradiol (EE) and 0.10 mg levonorgestrel (LNG) with potential advantages has been developed in China. This study was aimed to describe the pharmacokinetic characteristics of this new combination contraceptive tablet in female Chinese volunteers.

Methods: This study was designed as phase I, open-label, and one-sequence clinical trial. 12 healthy nonpregnant female Chinese volunteers received a single dose (1 tablet) and multiple dose (1 tablet per day) administration for 21 consecutive days under fasting condition. Blood samples were analyzed with 2 validated LC-MS/MS methods for EE and LNG, respectively.

Results and conclusion: After the single dose administration, the C _max of EE and LNG were 44.76±18.64 pg/mL and 2.256±1.008 ng/mL, respectively. The steady-state condition of EE was achieved on the 6^th day after the beginning of the multiple dose administration, while the steady-state condition of LNG was achieved on the 21^st day. For EE, the mean MRT _0–72 and t _1/2 increased by 40.2 and 30.6%, meanwhile the mean Cl/F and Vd/F decreased by 18.5 and 29.1%, respectively from Day 1 to Day 24. For LNG, the mean MRT _0–72 increased by 27.1%, while the mean Cl/F and Vd/F decreased by 62.4 and 86.3%, respectively from Day 1 to Day 24. The t _1/2 remained unchanged for LNG. The exposure of LNG significantly increased with repeated dosing, but that of EE just slightly increased.

Key words

ethinyl estradiol - levonorgestrel - LC-MS/MS - pharmacokinetics - sex hormone-binding globulins

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