PHARMACOKINETIC CHAR OF DILAUDID SR RELATIVE TO HYDROMORPHONE

DILAUDID SR 相对于氢吗啡酮的药代动力学特征

• 批准号: 6264315
• 负责人: DONALD R STANSKI
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264315
• 关键词: clinical research; drug administration routes; drug screening /evaluation; electroencephalography; human subject; injection /infusion; morphine; oral administration; pain; pharmacokinetics; slow release drug

The objectives of this three phase crossover PK/PD study of an open label design for phase one and two, and a double-blind, randomized design for phase three were as follows: 1) To characterize the pharmacokinetic profile of three hydromorphone formulations - Intravenous (IV), oral immediate release (IR), and new oral slow release (SR). 2) To test for the linearity of the pharmacokinetic profile of three geometrically increasing doses of the novel SR formulation. 3) To characterize the PK/PD relationship of IV hydromorphone for an EEG effect measure. 4) To characterize the PK/PD relationship of IR and SR hydromorphone for an analgesic effect measure. 5) To characterize the PK/PD relationship of SR hydromorphone for a subjective opioid effect measure. Twelve normal, healthy subjects (6 male and 6 female) participated and completed the study. The six study periods were separated by at least 7 days and consisted of a 24-h period for IV administration, a 24-h period for administration of IR-hydromorphone, and 4 periods each lasting 38-h for administration of 3 different doses of SR-hydromorphone and placebo, respectively. The pharmacokinetics were assessed by measuring serial arterial and venous hydromorphone concentrations. Compartment and non-compartmental analysis of the pharmacokinetics was performed. EEG was recorded for 6 hours after IV administration of hydromorphone. Experimental pain models were employed for 6 and 30 hours after oral administration of IR and SR hydromorphone, respectively, to quantify the analgesic efficacy. Side effects and effects on mood and mental condition were assessed with a brief, subjective opioid effects questionnaire.

该三阶段交叉PK/PD研究的目的如下：1）表征三种氢吗啡酮制剂-静脉内（IV）、口服立即释放（IR）和新的口服缓慢释放（SR）的药代动力学特征。2)检测三种几何递增剂量的新型SR制剂的药代动力学曲线的线性。3)表征IV氢吗啡酮的PK/PD关系，用于EEG效应测量。4)表征IR和SR氢吗啡酮的PK/PD关系，用于镇痛效果测量。5)表征SR氢吗啡酮的PK/PD关系，用于主观阿片效应测量。12名正常健康受试者（6名男性和6名女性）参与并完成了研究。6个研究阶段间隔至少7天，包括IV给药24小时、IR-氢吗啡酮给药24小时和SR-氢吗啡酮和安慰剂3种不同剂量给药各持续38小时的4个阶段。通过测量连续的动脉和静脉氢吗啡酮浓度来评估药代动力学。对药代动力学进行了房室和非房室分析。在静脉注射氢吗啡酮后6小时记录EEG。分别在口服IR和SR氢吗啡酮后6小时和30小时采用实验性疼痛模型来量化镇痛功效。副作用以及对情绪和精神状况的影响通过简短的主观阿片类药物作用问卷进行评估。