Buckheit Karen W, Buckheit Robert W
Topical Microbicide and STI Research Department, ImQuest BioSciences, Inc., 7340 Executive Way, Suite R, Frederick, MD 21704, USA.
Mol Biol Int. 2012;2012:781305. doi: 10.1155/2012/781305. Epub 2012 Jul 12.
Significant advancements in topical microbicide development have occurred since the prevention strategy was first described as a means to inhibit the sexual transmission of HIV-1. The lack of clinical efficacy of the first generation microbicide products has focused development attention on specific antiretroviral agents, and these agents have proven partially successful in human clinical trials. With greater understanding of vaginal and rectal virus infection, replication, and dissemination, better microbicide products and delivery strategies should result in products with enhanced potency. However, a variety of development gaps exist which relate to product dosing, formulation and delivery, and pharmacokinetics and pharmacodynamics which must be better understood in order to prioritize microbicide products for clinical development. In vitro, ex vivo, and in vivo models must be optimized with regard to these development gaps in order to put the right product at the right place, at the right time, and at the right concentration for effective inhibition of virus transmission. As the microbicide field continues to evolve, we must harness the knowledge gained from unsuccessful and successful clinical trials and development programs to continuously enhance our preclinical development algorithms.
自从预防策略首次被描述为一种抑制HIV-1性传播的手段以来，局部杀菌剂的开发取得了重大进展。第一代杀菌剂产品缺乏临床疗效，这使得研发重点集中在特定的抗逆转录病毒药物上，而这些药物在人体临床试验中已被证明取得了部分成功。随着对阴道和直肠病毒感染、复制及传播有了更深入的了解，更好的杀菌剂产品和给药策略应能带来效力更强的产品。然而，在产品剂量、配方与给药、药代动力学和药效学方面存在各种有待填补的研发空白，为了将杀菌剂产品列为临床开发的优先项目，必须对这些空白有更深入的了解。必须针对这些研发空白对体外、离体和体内模型进行优化，以便在正确的时间、正确的地点，以正确的浓度使用正确的产品，有效抑制病毒传播。随着杀菌剂领域不断发展，我们必须利用从失败和成功的临床试验及开发项目中获得的知识，不断改进我们的临床前开发算法。
