A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women
A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women
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DOI：
10.1097/qad.0000000000000280
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发表时间：
2014-06-19
期刊：
影响因子：
3.8
通讯作者：
van Niekerk, Neliette
中科院分区：
文献类型：
--
作者：
Nel, Annalene;Haazen, Wouter;van Niekerk, Neliette
目标：迫切需要妇女发起的艾滋病毒预防产品。为了满足这一需求，进行了一项试验，以评估含有25毫克抗逆转录病毒药物达匹维林的硅胶弹性体基质阴道环连续使用28天的安全性和药代动力学。方法：一项双盲、随机、安慰剂对照试验在16名18-40岁的健康hiv阴性女性中进行，她们被随机分为1∶1组，使用有效或匹配的安慰剂环，为期28天。参与者在环使用期间和使用后28天进行安全性和药代动力学评估。结果：达匹维林阴道环是安全的，耐受性良好，活性环和安慰剂环的安全终点没有差异。阴道液中达匹维林的浓度-时间图表明，达匹维林在使用28天内持续释放。达匹维尔林阴道液浓度在环附近最高，其次是子宫颈和阴道（平均C-max分别为80、67和31 μ g/g）。在组织外植体感染模型中，取环当天（第28天）三个收集点的阴道液中达匹维林浓度超过了达匹维林IC99的3900倍以上。血浆达匹维林浓度低(
Objectives: Women-initiated HIV-prevention products are urgently needed. To address this need, a trial was conducted to assess the safety and pharmacokinetics of a silicone elastomer matrix vaginal ring containing 25 mg of the antiretroviral drug dapivirine when used continuously for 28 consecutive days.Methods: A double-blind, randomized, placebo-controlled trial was conducted in 16 healthy, HIV-negative women, 18-40 years of age, who were randomized 1 : 1 to use either the active or matching placebo ring for 28 days. Participants were followed during and for 28 days after ring use for safety and pharmacokinetic evaluations.Results: The dapivirine vaginal ring was safe and well tolerated with no differences in safety endpoints between the active and placebo ring. The concentration-time plots of dapivirine in vaginal fluid were indicative of a sustained release of dapivirine over the 28 days of use. Dapivirine vaginal fluid concentrations were highest near the ring, followed by the cervix and introitus (mean C-max of 80, 67 and 31 mu g/g, respectively). Vaginal fluid concentrations of dapivirine on the day of ring removal (day 28) at all three collection sites exceeded by more than 3900-fold the IC99 for dapivirine in a tissue explant infection model. Plasma dapivirine concentrations were low (