Original research articlePharmacokinetics of subcutaneous depot medroxyprogesterone acetate injected in the upper arm☆
Introduction
A subcutaneous (SQ) lower-dose formulation of depot medroxyprogesterone acetate (DMPA), a widely used injectable contraceptive, is available in the United States, Europe and a number of other countries in a preloaded glass syringe [1]. The product in a prefilled glass syringe is marketed as Depo-SubQ Provera 104™ in the United States and as Sayana™ globally (Pfizer, Inc., New York, NY, USA). Through the collaborative efforts of the US Agency for International development, PATH, Becton Dickenson and Pfizer, the DMPA SQ formulation has been repackaged in an alternative delivery system, the Uniject™ device (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) [2]. Uniject is an autodisabled injection device developed to increase access to injectable medications in low-resource settings [3], [4]. DMPA SQ in the Uniject device (Depo-SubQ in Uniject or Sayana Press™) (Pfizer, Inc., New York, NY, USA) was granted marketing approval in Europe in 2011 and will be available for distribution in selected developing countries starting in 2013.
The current labeling for Depo-SubQ Provera 104 calls for injection in the abdomen or thigh [5]. However, for privacy reasons, the upper arm may be a preferred injection site in many developing countries. Some studies have demonstrated that the rates of absorption of some drugs may fluctuate according to the injection site [6], [7], while other, more recent studies have not shown this association [8], [9]. Given the inconsistent evidence seen with other medications, we designed a study to evaluate the pharmacokinetic (PK) profile of medroxyprogesterone acetate (MPA) and demonstrate that the blood levels of MPA following injection of Depo-SubQ Provera 104 in the upper arm are consistent with effective contraception for 3 months.
Section snippets
Materials and methods
This single-arm prospective trial was conducted at the Clinical Research Center, Department of Obstetrics & Gynecology, at the Eastern Virginia Medical School (Norfolk, VA) between June 2010 and June 2011. The Chesapeake Research Review’s Institutional Review Board and FHI 360’s Protection of Human Subjects Committee approved the study. Pfizer provided the drug but otherwise was not involved in the implementation of the study or interpretation of the results.
To be enrolled in the study, women
Results
Out of 26 women enrolled into the study, 24 women completed the study. Two women were lost to follow-up: one after day 14 and another after day 104. We excluded one participant from the final PK analysis for a nonzero serum MPA level at baseline (additional investigation found that this woman failed to report recent history of use for DMPA at the time of enrollment). As a result, 25 women contributed data to the primary analysis. Most participants (92%) completed at least 11 out of the 12e
Discussion
The mean concentrations of MPA remained well above 0.2 ng/mL for at least 91 days following the SQ injection in the upper arm. Based on these findings, similar to other pharmacokinetic/pharmacodynamic (PK/PD) studies of Depo-SubQ Provera 104 [11], [12], [13], we conclude that injection of Depo-SubQ Provera 104 into the upper arm provides sufficient serum levels of MPA for contraceptive protection for 3 months (13 weeks).
Strengths of our study include a simple design, use of a validated highly
Acknowledgments
Pfizer provided the study drug but otherwise was not involved in the implementation of the trial or interpretation of the results.
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This trial was funded by the United States Agency for International Development.