Pharmacokinetics of the 1.5mg levonorgestrel emergency contraceptive in women with normal, obese and extremely obese body mass index.

OBJECTIVE: To assess the pharmacokinetics (PK) of levonorgestrel after 1.5mg oral doses (LNG-EC) in women with normal, obese and extremely obese body mass index (BMI).

STUDY DESIGN: The 1.5mg LNG dose was given to healthy, reproductive-age, ovulatory women with normal BMI (mean 22.0), obese (mean 34.4), and extremely obese (mean 46.6kg/m2 ) BMI. Total serum LNG was measured over 0 to 96h by radioimmunoassay while free and bioavailable LNG were calculated. The maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC) of LNG were assessed. Pharmacokinetic parameters calculated included half-life (t1/2), clearance (CL) and volume of distribution (Vss).

RESULTS: Ten normal-BMI, 11 obese-BMI, 5 extremely obese-BMI women were studied. After LNG-EC, mean total LNG metrics were lower in the obese and extremely obese groups compared to normal (Cmax 10.5 and 10.5 versus 16.2ng/mL, both p<.01; AUC 208 and 197 versus 360h×ng/mL, both p<.05). Mean bioavailable LNG Cmax was lower in obese (7.03ng/mL, p<.05) and extremely obese (7.53ng/ml, p=.198) compared to normal BMI (9.39ng/mL). Mean bioavailable LNG AUC values were lower in obese and extremely obese compared to normal (131.6 and 127.5 vs 185.0h×ng/mL, p<.05 for both).

CONCLUSIONS: Obese and extremely obese women were exposed to lower total and bioavailable LNG than normal BMI women. Implications Lower 'bioavailable' (free plus albumin bound) LNG AUC in obese women may play a role in the purported reduced efficacy of LNG-EC in obese users.