EVAL OF PHRMACOKIN INTERACTIONS BETWEEN CRESTOR&COMBO PROTEASE INHIBITOR KALETRA

CRESTOR 之间 PHRMACOKIN 相互作用的评估

• 批准号: 7377863
• 负责人: DORIE W HOODY
• 金额: $ 19.74万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377863
• 关键词: EVAL; PHRMACOKIN; INTERACTIONS; BETWEEN; CRESTOR&COMBO

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. The primary objective of this study protocol is to compare the drug disposition of the cholesterol lowering drug rosuvastatin in the absence and presence of the anti-HIV combination drug product lopinavir/ritonavir. This is an important study because anti-HIV medications can cause lipid alterations in persons who receive them. The medications on the market that treat hyperlipidemia are potent, effective agents. However, most of them are metabolized by the same pathway in the liver as anti-HIV medications, which can lead to toxicities in patients taking these drugs together. Evidence supports that rosuvastatin is not metabolized by the same route as the anti-HIV medications, and it is a potent lipid lowering drug. Therefore, patients with HIV would benefit from being able to receive concomitant therapy of rosuvastatin with their anti-HIV medications. The study is designed as an open label, single-arm, crossover pharmacokinetic study. Healthy volunteers will be recruited to participate over a 24-day period. There are three phases to the study after study participants have been screened and are determined to be eligible for participation. The first phase involves administration of rosuvastatin beginning on Study Day 0 and through Study Day 6. On Study Day 6, participants will be admitted into the inpatient GCRC where they will have serial blood draws to determine the pharmacokinetics of rosuvastatin during the 24-hour dosing interval without anti-HIV medications on board. The serial blood draws will begin immediately prior to an observed dose of drug. The second phase of the study will begin on Study Day 7. Study participants will be dispensed the combination product lopinavir/ritonavir and begin taking it every twelve hours for the remainder of their participation. On study day 16, participants will be admitted into the inpatient GCRC where they will have serial blood drawn to determine the pharmacokinetics of lopinavir/ritonavir, during the 12-hour dosing interval without rosuvastatin on board. The serial blood draws will begin immediately prior to an observed dose of the lopinavir/ritonavir. The third and final phase of the study will begin on study day 17, when study participants will add rosuvastatin once daily and continue taking lopinavir/ritonavir every 12-hours. The study participants will return to the inpatient GCRC on study day 23, where serial blood draws will begin immediately prior to an observed dose of both study drugs and continue over 24 hours. There are two secondary objectives to this study. (1) we will also measure levels of lopinavir/ritonavir make sure rosuvastatin is not affecting its metabolism, and (2) blood lipid panels will be drawn at each study visit to see if there is a clinical effect on cholesterol-lowering capabilities of rosuvastatin when it is administered in combination with lopinavir/ritonavir. Finally, safety labs will be drawn during each study visit to minimize risk to study participants. Pill counts and a verbal and written adherence evaluation will be conducted at study visits to ensure that study procedures are being complied with by the volunteers.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。本研究方案的主要目的是比较在不存在和存在抗 HIV 组合药物洛匹那韦/利托那韦的情况下降胆固醇药物瑞舒伐他汀的药物处置。这是一项重要的研究，因为抗艾滋病毒药物可能会导致接受药物的人的血脂发生变化。市场上治疗高脂血症的药物是强效、有效的药物。然而，它们中的大多数在肝脏中通过与抗艾滋病毒药物相同的途径代谢，这可能会导致患者同时服用这些药物时出现毒性。有证据表明，瑞舒伐他汀的代谢途径与抗 HIV 药物不同，它是一种有效的降脂药物。因此，艾滋病毒患者将受益于瑞舒伐他汀与抗艾滋病毒药物的联合治疗。 该研究被设计为开放标签、单臂、交叉药代动力学研究。将招募健康志愿者参与为期 24 天的活动。研究参与者经过筛选并确定有资格参与后，研究分为三个阶段。第一阶段包括从研究第 0 天开始直至研究第 6 天给予瑞舒伐他汀。在研究第 6 天，参与者将被送入住院 GCRC，在那里他们将进行连续抽血以确定瑞舒伐他汀在 24 小时给药间隔期间的药代动力学，而船上没有抗 HIV 药物。连续抽血将在观察药物剂量之前立即开始。 研究的第二阶段将于研究第 7 天开始。研究参与者将获得洛匹那韦/利托那韦组合产品，并在剩余的参与期间开始每 12 小时服用一次。在研究第 16 天，参与者将被送往住院 GCRC，在那里他们将进行连续抽血以确定洛匹那韦/利托那韦的药代动力学，在 12 小时的给药间隔期间，没有瑞舒伐他汀在场。连续抽血将在洛匹那韦/利托那韦观察剂量之前立即开始。 研究的第三阶段也是最后阶段将于研究第 17 天开始，届时研究参与者将每天添加一次瑞舒伐他汀，并继续每 12 小时服用洛匹那韦/利托那韦。研究参与者将在研究第 23 天返回住院 GCRC，在观察两种研究药物剂量之前立即开始连续抽血，并持续超过 24 小时。 这项研究有两个次要目标。 (1) 我们还将测量洛匹那韦/利托那韦的水平，确保瑞舒伐他汀不会影响其代谢，(2) 每次研究访视时都会进行血脂检测，以了解瑞舒伐他汀与洛匹那韦/利托那韦联合用药时是否对降低胆固醇能力产生临床效果。最后，将在每次研究访问期间绘制安全实验室，以尽量减少研究参与者的风险。在研究访问时将进行药丸计数以及口头和书面依从性评估，以确保志愿者遵守研究程序。