PI-114

J. Shon, L. Li, M. Kim; US Food and Drug Administration, Silver Spring, MD

BACKGROUND: Levonorgestrel containing emergency contraceptives (LNG-EC) are used to prevent unintended pregnancy in women of all body weights (BW). The available pharmacokinetics (PK) data are limited to address how BW affects the systemic exposure of LNG-EC. This study assessed the effects of BW and body mass index (BMI) on the disposition of LNG after a single dose of LNG-EC in healthy women.
METHODS: Two phase I PK studies were identified from the new drug applications submitted to US FDA. The demographic data and the PK parameters of LNG in 44 subjects who took a single dose of LNG 1.5 mg were retrieved. The groups were classified according to the BW (<60kg, 60-70kg, ≥70kg) and BMI (< 25 kg/m2, ≥25 kg/m2). The effects of BW/BMI on the PK of LNG were evaluated with ANOVA analysis. A linear regression analysis between BW/BMI and the log-transformed values of Cmax and AUC was performed.
RESULTS: The PK of LNG-EC were available only in women of normal BW or overweight because the study inclusion criteria limited the BMI < 30kg/m2. A BW/BMI-dependent distribution tendency was observed of Cmax and AUC of LNG. The overweight group (≥25kg/m2) showed lower mean AUC and Cmax by 40% and 31%, respectively, compared to those with BMI <25kg/m2. A large inter-individual variability was observed in each BW/BMI group.
CONCLUSION: The currently available PK data showed that there is a trend of decreasing exposure of LNG after a single dose administration of LNG 1.5 mg in overweight women. The clinical implication of decreased LNG-EC exposure is not clear. Further research is needed to address the potential public health consequences.