Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1.5 mg for emergency contraception.

BACKGROUND: Progestin-only methods are among the contraceptive options available for breastfeeding women, however the doses of progestin used in emergency contraception (EC) have not been evaluated in nursing mothers. We therefore investigated the pharmacokinetics of 1.5 mg levonorgestrel (LNG) in lactating women. METHODS: Twelve healthy exclusively breastfeeding volunteers received 1.5 mg LNG. Women refrained from nursing for 72 h after dosing and fed their infants with milk frozen beforehand. Serial blood and milk samples were collected for 120 h and assayed for LNG and sex hormone binding globulin. RESULTS: LNG concentrations peaked in plasma and in milk 1-4 h and 2-4 h after dosing, respectively. Concentrations in milk (M) paralleled those in plasma (P) but were consistently lower (mean M:P ratio 0.28). Estimated infant exposure to LNG is 1.6 microg on the day of dosing (1 microg in the first 8 h), 0.3 microg on the second day and 0.2 microg on the third day. CONCLUSIONS: Nursing mothers may need EC. These results suggest that to limit infant exposure to the period of maximum LNG excretion in milk, mothers should discontinue nursing for at least 8 h, but not more than 24 h, after EC.

Pharmacokinetics of levonorgestrel 0.75 mg tablets.

This study examined plasma levonorgestrel (LNG) concentrations and pharmacokinetics following oral administration of a single LNG 0.75 mg tablet. Sixteen healthy female volunteers 19-44 years old enrolled in the study. Serial blood samples were drawn over 72 h after dosing in a fasting state. A gas chromatographic, negative ionization mass spectrometric detection analytical method was used to determine plasma LNG concentrations. The observed mean peak plasma LNG concentration was 14.1 +/- 7.9 ng/mL (range 6.7-39.0 ng/mL). The mean time of peak concentration was 1.63 +/- 0.74 h (range 1-4 h). The plasma LNG concentration versus time profiles were subjected to noncompartmental pharmacokinetic analysis for the purposes of determining half-lives, apparent oral clearances (Cl/F), apparent volumes of distribution after oral administration (V/F), and mean residence time (MRT). Half-lives calculated from the terminal decline in plasma LNG concentrations ranged from 16.2 h to 32.3 h (mean = 24.4 +/- 5.3 h). The Cl/F was 7.06 +/- 2.69 L/h, V/F was 260 +/- 129 L, and MRT was 27.8 +/- 5.2 h. LNG was well tolerated; there were no serious adverse events during the study.

The pharmacokinetics of 750 microg levonorgestrel following administration of one single dose or two doses at 12- or 24-h interval.

The administration of two tablets of 750 microg levonorgestrel at a 12- to 24-h interval has been shown to be a safe and effective means of emergency contraception, and Norlevo/Vikela (N/V) is a dedicated product for this indication. The aim of this study was to characterize the plasma pharmacokinetics of levonorgestrel following a single N/V tablet administration and following a second administration, 12 or 24 h after the first one in young, healthy, female volunteers under the same conditions as during clinical use. This was an open, observer-blind, randomized study with three parallel groups and three treatments performed in 24 white female volunteers randomized into three groups of eight participants, each receiving one of the following treatments: Group A, one tablet of 750 microg levonorgestrel at time -12 h and one tablet at time 0; Group B, one tablet of 750 microg levonorgestrel at time 0; Group C, one tablet of 750 microg levonorgestrel at time -24 h and one tablet at time 0. All treatments started between Day 2 and Day 6 of the menstrual cycle. Plasma levonorgestrel levels were measured at regular intervals from time 0 up to 36 h with a validated radioimmunoassay. The results of this study show that after either one single or two administrations of a tablet containing 750 microg levonorgestrel, levonorgestrel is rapidly absorbed. The absorption, distribution, and elimination profiles of levonorgestrel following the three different treatments were similar. It also indicates that 12 or 24 h after administration there remains a significant level of plasma levonorgestrel. In conclusion, this study reinforces clinical guidelines recommending that N/V tablets for emergency contraception be administered 12 to 24 h apart because levonorgestrel is present in plasma between the two administrations.