title: In vivo release of levonorgestrel from Sino-implant (II) — an innovative comparison of explant data.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates 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 release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: FHI 360, Durham, NC 27701, USA. Electronic address: rcallahan@fhi360.org.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Callahan
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Taylor
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Jenkins
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Owen
authors.affiliation: Shanghai Institute of Planned Parenthood Research (SIPPR), Shanghai, China.
authors.forename: Linan
authors.initials: L
authors.lastname: Cheng
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Cancel
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: Laneta J
authors.initials: LJ
authors.lastname: Dorflinger
authors.affiliation: FHI 360, Durham, NC 27701, USA.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Steiner
mesh_terms: D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D003271:Contraceptive Agents, Female; D016912:Levonorgestrel
keywords: China; Contraceptive implant; Explant; Jadelle; Sino-implant (II)