Basic/Translational Investigations on Buprenorphine

项目摘要 丁丙诺啡的基础/转化研究 丁丙诺啡治疗是药物滥用障碍患者的一种治疗选择。 丁丙诺啡通常舌下施用，并且丁丙诺啡的剂量滴定至在体内的反应。 个别科目。孕妇似乎需要更高剂量的丁丙诺啡相比，非 孕妇我们提议的基础/转化研究将补充提议的临床研究， 提供通常无法在孕妇中获得的机械信息和数据。我们将研究 妊娠对孕鼠处理丁丙诺啡的影响 怀孕的老鼠。我们还将研究丁丙诺啡如何改变大脑中的各种内源性化学物质 因此对丁丙诺啡也有反应由于患者长期接受丁丙诺啡治疗， 胎盘往往积累了大量的丁丙诺啡，我们也将评估丁丙诺啡的影响， 与未服用丁丙诺啡的孕妇相比， 丁丙诺啡我们还将研究胎儿肝脏代谢任何丁丙诺啡的能力， 胎盘我们还计划使用计算机模拟来预测暴露于 丁丙诺啡在母亲和胎儿在怀孕期间的不同时间点。我们的研究将 帮助优化孕妇丁丙诺啡的剂量，并尽量减少不遵守这一重要的 治疗选择

PROJECT SUMMARY Basic/Translational Investigations on Buprenorphine Treatment with buprenorphine is a therapeutic option for patients with substance abuse disorders. Buprenorphine is normally administered sublingually and the dose of buprenorphine is titrated to a response in individual subjects. Pregnant women appear to require a higher dose of buprenorphine compared to non- pregnant women. Our proposed basic/translational studies will complement the clinical study proposed and provide mechanistic information and data that cannot be normally obtained in pregnant women. We will study the effect of pregnancy on how buprenorphine in handled in pregnant using pregnant rats and isolated livers from pregnant rats. We will also study how buprenorphine alters various endogenous chemicals in the brain and hence the response to buprenorphine. Since patients are on chronic therapy with buprenorphine and placenta tends to accumulate a lot of buprenorphine, we will also evaluate the impact of buprenorphine on various enzymes and proteins in the placenta of pregnant women on buprenorphine in comparison to those not on buprenorphine. We will also study the ability of the fetal liver to metabolize any buprenorphine that crosses the placenta. We also plan to use computer simulations to predict what will happen to exposure of buprenorphine in the mother and fetus at various time points during pregnancy. Collectively our studies will help optimize dosing of buprenorphine in pregnant women and minimize non-adherence to this important treatment option.