Fuchs Rachael, Taylor Douglas, Jenkins David W, Brache Vivian, Luo Diane, Dorflinger Laneta J, Steiner Markus J
FHI 360, 359 Blackwell St. Suite 200, Durham, NC 27701, USA.
Asociación Dominicana Pro Bienestar de la Familia, Inc. (PROFAMILIA), Santo Domingo, Dominican Republic.
Contracept X. 2020 Aug 21;2:100039. doi: 10.1016/j.conx.2020.100039. eCollection 2020.
The objective was to characterize and compare in vivo rates of levonorgestrel (LNG) release from Sino-implant (II) and Jadelle® contraceptive implants.
We sampled 48 Sino-implant (II) and 49 Jadelle® explant sets for residual LNG content from participants treated for up to 51 months in a randomized contraceptive efficacy trial in the Dominican Republic (DR). Additional Sino-implant (II) explants were obtained from 8 women who became pregnant in the DR trial and 10 who contributed 3 to 5 years of use in a cohort study in China. Baseline LNG loads were estimated from five unused implant sets per device type. Release profiles were estimated using mixture models that captured initial burst fractions and compared with efficacy and pharmacokinetics data from the DR trial.
Estimated baseline LNG loads for Sino-implant (II) and Jadelle® were 142.8 mg and 150.5 mg, respectively (vs. the labeled 150 mg). There was an initial burst release of drug (5.6% and 7.9%, respectively) followed by an exponential decrease in LNG content evident for each device. Release rates were significantly lower for Sino-implant (II) throughout the treatment period, with estimated rates after 3 years of 24.2 mcg/day and 29.0 mcg/day for Sino-implant (II) and Jadelle®, respectively. The estimated Sino-implant (II) rate after 3 years was similar to the predicted rate after 5 years (23.6 mcg/day) for Jadelle® (rate ratio: 1.03; 95% confidence interval: 0.92-1.13).
Sino-implant (II) LNG release rates were significantly lower than Jadelle® with Sino-implant (II) rates through year 3 comparable to Jadelle® rates through year 5. These results reinforce the 3-year duration of action for which Sino-implant (II) was prequalified by the World Health Organization.
This analysis confirms the WHO prequalification of Sino-implant (II) for 3 years of use and supports different durations of action for Jadelle® and Sino-implant (II). It provides additional evidence that this approach can complement efficacy trials in determining duration of action of hormonal contraceptives in general.
本研究旨在表征和比较左炔诺孕酮（LNG）从中国皮下埋植剂（II型）（Sino-implant (II)）和杰德勒皮下埋植剂（Jadelle®）中的体内释放率。
在多米尼加共和国（DR）进行的一项随机避孕效果试验中，我们从接受治疗长达51个月的参与者中采集了48套中国皮下埋植剂（II型）和49套杰德勒皮下埋植剂的取出物，用于检测残留LNG含量。另外，从DR试验中怀孕的8名女性以及在中国进行的一项队列研究中使用了3至5年的10名女性身上获取了额外的中国皮下埋植剂（II型）取出物。根据每种器械类型的五套未使用的埋植剂估算基线LNG含量。使用混合模型估算释放曲线，该模型捕捉了初始突释部分，并与DR试验中的效果和药代动力学数据进行比较。
中国皮下埋植剂（II型）和杰德勒皮下埋植剂的估算基线LNG含量分别为142.8毫克和150.5毫克（与标示的150毫克相比）。每种器械都有药物的初始突释（分别为5.6%和7.9%），随后LNG含量呈指数下降。在整个治疗期间，中国皮下埋植剂（II型）的释放率显著较低，中国皮下埋植剂（II型）和杰德勒皮下埋植剂在3年后的估算释放率分别为每天24.2微克和29.0微克。中国皮下埋植剂（II型）在3年后的估算释放率与杰德勒皮下埋植剂在5年后的预测释放率（每天23.6微克）相似（率比：1.03；95%置信区间：0.92 - 1.13）。
中国皮下埋植剂（II型）的LNG释放率显著低于杰德勒皮下埋植剂，中国皮下埋植剂（II型）在3年内的释放率与杰德勒皮下埋植剂在5年内的释放率相当。这些结果强化了世界卫生组织对中国皮下埋植剂（II型）预先认定的3年作用持续时间。
本分析证实了世界卫生组织对中国皮下埋植剂（II型）3年使用期限的预先认定，并支持杰德勒皮下埋植剂和中国皮下埋植剂（II型）有不同的作用持续时间。它提供了额外的证据，表明这种方法一般可补充疗效试验以确定激素避孕药的作用持续时间。
