MORPHINE PHARMACOKINETICS AND PHARMACODYNAMICS IN SICKLE CELL DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 医疗保健提供者对阿片类药物成瘾的认识和关注可能是适当护理的主要障碍。此外，在SCD中使用有时高剂量的阿片类药物用于急性和慢性疼痛管理已经导致了对不适当的阿片类药物依赖和成瘾的担忧。 这项研究解决了缺乏支持性证据，以确定适当的阿片类药物处方在SCD，我们提出了一个基本的试点研究，以表征吗啡的药代动力学和药效学在我们的SCD人群的部分。 这项试点研究将大大告知镰状细胞社区，并为更大规模的阿片类药物用于SCD试验奠定基础 采用剂量反应设计，在3组中确定吗啡（IV和PO）的药代动力学（吗啡-3-葡糖苷酸（M3 G）和吗啡-6-葡糖苷酸（M6 G））和药效学（主观、认知、心血管和镇痛）效应： 1.未长期接受阿片类药物治疗的镰状细胞病患者， 2.接受长期阿片类药物治疗的镰状细胞病患者， 3.对照非裔美国人参与者没有物质使用障碍或目前使用阿片类药物，年龄，种族，性别和体重相匹配。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Healthcare providers' perception of and concern regarding opiate addiction can be major barriers to appropriate care. Further, use of sometimes high doses of opiates for acute and chronic pain management in SCD has led to concerns of inappropriate opiate dependence and addiction. This study address the lack of supportive evidence for determining appropriate opiate prescribing in SCD, we propose a basic pilot study to characterize the pharmacokinetics and pharmacodynamics of morphine in segments of our SCD population. This pilot study will greatly inform the sickle cell community and prepare the ground for larger scale trials of opioid use in SCD To determine the pharmacokinetic (morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and pharmacodynamic (subjective, cognitive, cardiovascular and analgesic) effects of morphine (IV and PO) using a dose response design in 3 groups: 1. Sickle cell disease patients not treated chronically with opioids, 2. Sickle cell disease patients receiving chronic opioid treatment, 3. Control African-American participants without substance use disorders or current opioid use matched by age, race, gender, and weight.