Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): effects of body weight and injection sites on pharmacokinetics.

Abstract

A new contraceptive option, medroxyprogesterone acetate (MPA) and estradiol cypionate (E2C) (MPA/E2C, Lunelle Monthly Contraceptive Injection), will soon be available for women in the US. This article reports the results of a US trial that assessed the effects of body weight and injection site on the pharmacokinetics of MPA, the progestin mediating contraceptive efficacy. This assessment was part of a nonrandomized, open-label, multicenter US study in healthy women receiving a monthly injection of MPA/E2C for 60 weeks. A total of 77 women (aged 18-47 years) at four centers participated in the pharmacokinetics assessment during the sixth or the seventh injection. For determination of serum MPA concentration-time profiles, blood samples were collected before the sixth and seventh injections (day 0) and on days 3, 7, 14, 21, and 28 after the sixth and seventh monthly administrations. For effects of injection site, MPA pharmacokinetics were compared at injection sites of the arm, hip, and leg. The pharmacokinetics of MPA, determined at the sixth and seventh injection, were not significantly affected by injection sites. The mean area under the curve (AUC0-28), however, was different between the arm and the leg injection sites; the difference was < 20%. More important, the average MPA trough concentrations (Cmin) at the fifth and sixth monthly injections were similar (range 0.42-0.51 ng/mL) for the three injection sites and well above the threshold levels of 0.10-0.20 ng/mL required to suppress ovulation. For effects of body mass index (BMI) on pharmacokinetics, women were stratified into three groups: thin/normal (BMI 18-28, n = 48), obese (BMI 29-38, n = 23), and highly obese (BMI > 38, n = 6). There were no significant differences in the pharmacokinetics of MPA among the three BMI categories. The only significant difference (p = 0.0387) was the AUC0-28 between BMI 18-28 and BMI 29-38. Because of the small sample size in the highly obese group, a reanalysis was performed by pooling subjects of the obese and highly obese groups. Results of the pooled statistical analysis remained the same. In summary, these results suggest that minor differences observed in the MPA pharmacokinetics--whether due to injection site or body weight or both--have no impact on the contraceptive efficacy of MPA/E2C, as trough concentrations (Cmin) are well above the threshold levels required to suppress ovulation. No dose adjustment is necessary based on body weight or injection site.