Basic/Translational Investigations on Buprenorphine

丁丙诺啡的基础/转化研究

• 批准号: 9119109
• 负责人: Raman Venkataramanan
• 金额: $ 22.83万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9119109
• 关键词: Address; Adult; Age; Animal Model; Basic Science; Biliary; Biology; Brain; Buprenorphine; Cell Culture Techniques; Chemicals; Chronic; Clinical Research; Collaborations; Complement; Computer Simulation; Data; Dealkylation; Disease; Dose; Drug Exposure; Drug Kinetics; Enzymes; Exposure to; Fetal Liver; Fetus; Glucuronides; Hepatic; Hepatocyte; Human; Individual; Intestines; Investigation; Liver; Metabolism; Mothers; Neurotransmitters; Obstetric Fetal Pharmacology; Opioid; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Placenta; Plasma; Pregnancy; Pregnant Women; Proteins; Race; Rattus; Research; Serotonin; Substance abuse problem; Therapeutic; Time; Translational Research; Universities; base; education research; fetal; in vivo; models and simulation; multidisciplinary; neurobehavioral; neurochemistry; pharmacokinetic model; pregnant; response; translational study

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.

项目总结