MORPHINE PHARMACOKINETICS AND PHARMACODYNAMICS IN SICKLE CELL DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 医疗保健提供者对阿片成瘾的看法和担忧可能是适当护理的主要障碍。此外，在SCD中使用有时大剂量的阿片类药物来治疗急性和慢性疼痛导致了人们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确定SCD患者适当阿片类药物处方的支持证据的问题，我们建议进行一项基本的先导性研究，以表征吗啡在SCD人群中的药代动力学和药效学。这项先导性研究将极大地向镰状细胞群体提供信息，并为在SCD中进行更大规模的阿片类药物使用试验奠定基础。 采用剂量反应设计确定吗啡(IV和PO)的药代动力学(吗啡-3-葡萄糖醛酸苷(M3G)和吗啡-6-葡萄糖醛酸苷(M6G))和药效学(主观、认知、心血管和镇痛)作用。 1.未长期使用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.控制没有药物使用障碍或当前阿片类药物使用与年龄、种族、性别和体重匹配的非裔美国人参与者。

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.