Original research article In vivo release of levonorgestrel from Sino-implant (II) — an innovative comparison of explant data ☆,☆☆

Objectives: Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. Study design: We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results werecomparedwithpublisheddataforJadelleexplantsusedforupto36months.WeestimatedandcomparedmonthlyanddailyLNGreleaserates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. Results: Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8–85.7) indicates similarity in the dissolution profiles of the two implants. Conclusions: LNG releaseinvivomeasuredthroughexplantanalysissuggestthatSino-implant(II)andJadellemayperformsimilarlythrough3years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. Implications: This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants. © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).