Influence of Ritonavir, and Lopinavir/ritonavir on fenofibrate pharmacokinetics

利托那韦和洛匹那韦/利托那韦对非诺贝特药代动力学的影响

• 批准号: 8565308
• 负责人: Scott Penzak
• 金额: --
• 依托单位: CLINICAL CENTER
• 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/8565308
• 关键词: Adverse event; Anorexia; Cholesterol; Constipation; Dose; Drug Kinetics; Dyspepsia; Fenofibrate; Flushing; Headache; Institutional Review Boards; Lopinavir; Lopinavir/Ritonavir; Pharmaceutical Preparations; Reporting; Ritonavir; Safety; Sampling Studies; Secondary to; Serious Adverse Event; Study Subject; experience; fenofibric acid; follow-up; healthy volunteer; safety study

All thirteen subjects have completed this pharmacokinetic study. Pharmacokinetic samples from this study are currently being analyzed; however, to date there are no results available. With regard to safety, one subject experienced Grade 3 transaminitis secondary to treatment with lopinavir/ritonavir (LPV/r) that resolved when the drug was withdrawn secondary to study completion. This resulted in 2 Serious Adverse Event reports to the IRB (including the follow-up report, explaining that the transaminitis resolved). Of note, we have had no repeat problems of marked transaminitis in our study subjects. One subject experienced Grade 1 indigestion and bloating; another experienced Grade 1 flushing and Grade 2 constipation; and a third subject experienced Grade 1 headache and anorexia. These adverse events were possibly related to the study medications. Lastly, one subject experienced a Grade 2 increase in total cholesterol (from 198 mg/dL at baseline to 275 mg/dL) that was noted at end-of-study safety labs and likely due to lopinavir-ritonavir administration. No other increases in cholesterol have been noted thus far in this study.

所有13名受试者均完成了这项药代动力学研究。目前正在分析这项研究的药代动力学样本；但是，迄今为止尚无结果。关于安全性，一名受试者经历了继发于Lopinavir/Ritonavir（LPV/R）继发于治疗的3级跨动脉炎，该治疗是在撤回该药物中以进行研究完成时解决的。这导致了2个严重的不良事件向IRB报告（包括后续报告，解释了跨动脉炎已解决）。值得注意的是，我们在研究对象中没有重复出现明显的跨动炎的问题。一名受试者经历了1年级的消化不良和腹胀；另一个经验丰富的1级冲洗和2级便秘；第三个受试者经历了1级头痛和厌食症。这些不良事件可能与研究药物有关。最后，一名受试者的总胆固醇（从基线的198 mg/dL到275 mg/dl）的总胆固醇增加了2级，这在研究结束的安全实验室中被指出，可能是由于lopinavir-ritonavir给药而引起的。迄今为止，在这项研究中，胆固醇的其他升高还没有注意到。