SANTA FE, New Mexico (EGMN) – A single application of tenofovir 1% vaginal gel in term pregnancy produces low serum levels consistent with those reported in nonpregnant women, results from a small single-center trial demonstrated.

The findings come just weeks after a study that was published online in the journal Science found that 1% tenofovir gel used before and after sexual intercourse reduced HIV in women by 39% and reduced the incidence of herpes simplex virus type 2 infections by 50% (Science 2010 July 20 [doi:10.1126/science.1193748]).

“It does appear that tenofovir gel, once absorbed, does get to the fetal compartment, with very low overall cord blood levels – approximately 40-fold lower than you see after oral dosing – with a very similar cord:maternal blood ratio,” Dr. Richard Beigi said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

“In addition, it appears that single-dose tenofovir appears very safe in term pregnancy. These findings justify continued investigation of this product in pregnancy,” he said.

In a phase I trial conducted by the Microbicide Trials Network, researchers evaluated 16 healthy pregnant women who were scheduled to undergo cesarean delivery at term gestation between August 2008 and January 2010. The women received a single 4-g application of tenofovir 1% vaginal gel preoperatively.

“Oral tenofovir has a growing record of safety,” he said. “It’s a category B drug, with close to 1,000 exposures collected in the Antiretroviral Pregnancy Registry. So we felt very comfortable moving [the gel form of] this drug into pregnancy trials.”

Dr. Beigi of the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and his associates collected maternal blood for serum drug concentrations at baseline and at 1, 2, 4, 6, 8, 12, and 24 hours. They also collected specimens of amniotic fluid, cord blood, placenta, and endometrium during surgery, and collected data on maternal and neonatal adverse events.

All 16 women had detectable levels in the serum after vaginal placement. The median maternal concentration of tenofovir was 4.3 ng/mL, “which is very low,” Dr. Beigi said. “The median time to get that concentration was approximately 4 hours. To put this in perspective, when a mom takes a single oral dose of 600-mg tenofovir, their median concentration is 440 ng/mL. So we’re looking at levels that are approximately 100-fold lower.”

The median cord:maternal blood ratio was 0.53, which is approximately the same as with oral dosing of tenofovir.

There were very few serious adverse events among mothers and neonates, and none of them was considered to be related to tenofovir gel exposure. “On safety, we have no concerning signals at all,” Dr. Beigi said.

The study was funded by the U.S. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the U.S. National Institute of Mental Health. The nonprofit organization CONRAD supplied the tenofovir gel. Dr. Beigi said that he had no relevant financial disclosures to make.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

美国新墨西哥州圣大菲(EGMN)——一项试验表明，足月妊娠妇女单次使用替诺福韦1%阴道凝胶所产生的血药水平与该药用于非妊娠期妇女所报告的结果一致。

 

几周前，《科学》(Science)杂志在线发表的一项研究显示，替诺福韦1%阴道凝胶用于性交前后可将妇女感染HIV的几率降低39%，还能使2型单纯疱疹病毒感染的发生率降低50%(Science 2010 July 20 [doi:10.1126/science.1193748])。

 

妇产科传染病协会2010年年会上，美国匹兹堡大学妇产与生殖医学系的Richard Beigi博士说：“替诺福韦阴道凝胶一旦被人体吸收，的确会进入宫腔，但总的脐血水平非常低，大约只有口服给药后的1/40，脐血/母血比值则非常接近。目前已有越来越多的数据证实口服替诺福韦的安全性。替诺福韦属于妊娠期B类用药，这是基于抗逆转录病毒药物妊娠登记库所收集到的近1,000例暴露数据来确定的。因此我们并不担心该药的凝胶制剂用于妊娠期试验的安全性。”

 

在由杀菌剂试验网络开展的一项I期试验中，研究者对16例计划在2008年8月~2010年1月经足月妊娠后接受剖宫产的健康孕妇进行了评价。受试者在术前使用了替诺福韦1%阴道凝胶，用量为4 g。Beigi博士及其同事分别在基线、用药后1、2、4、6、8、12和24 h采集母体血液以测定血清药物浓度。研究者还在手术过程中采集了羊水、脐血、胎盘和子宫内膜样本，也收集了有关产妇和新生儿不良事件的数据。

 

经阴道给药后，在所有16例受试者中都检测到了血药浓度。替诺福韦的中位母体浓度非常低，只有4.3 ng/mL。“达到这一浓度的中位时间大约为4 h。相比之下，如果产妇单次口服替诺福韦600 mg，那么中位血药浓度是440 ng/mL，这比阴道凝胶给药后的浓度高了100多倍。”中位脐血/母血比值为0.53，这与替诺福韦口服给药后的测值几乎相同。无论是产妇还是新生儿，严重不良事件的发生率都非常低，并且均被视为与替诺福韦凝胶暴露无关。

 

该试验由美国国家过敏与传染病研究所、Eunice Kennedy Shriver国家儿童健康与人类发展研究所以及美国国家心理健康研究所共同资助。非盈利组织CONRAD提供了试验所使用的替诺福韦凝胶。Beigi博士表示无相关经济利益冲突。

 

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