EVAL OF PHRMACOKIN INTERACTIONS BETWEEN CRESTOR&COMBO PROTEASE INHIBITOR KALETRA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究方案的主要目的是比较降胆固醇药物瑞舒伐他汀在缺乏和存在抗hiv联合药物产品洛匹那韦/利托那韦时的药物配置。这是一项重要的研究，因为抗艾滋病毒药物可以导致接受这些药物的人的脂质改变。市场上治疗高脂血症的药物都是强效的药物。然而，它们中的大多数在肝脏中与抗hiv药物通过相同的途径代谢，这可能导致患者同时服用这些药物时产生毒性。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能够接受瑞舒伐他汀与抗艾滋病毒药物的联合治疗。该研究设计为一项开放标签、单臂、交叉药代动力学研究。健康志愿者将被招募参加为期24天的研究。在研究参与者被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天开始到研究第6天给药瑞舒伐他汀。在研究第6天，参与者将进入住院GCRC，在那里他们将进行连续抽血，以确定24小时给药间隔期间瑞舒伐他汀的药代动力学，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。研究的第二阶段将在第7天开始。研究参与者将被分配联合产品洛匹那韦/利托那韦，并开始每12小时服用一次，在他们的剩余参与。在研究第16天，参与者将进入住院GCRC，在12小时的给药间隔期间，他们将被连续抽血以确定洛匹那韦/利托那韦的药代动力学，船上没有瑞舒伐他汀。连续抽血将在洛匹那韦/利托那韦观察剂量之前立即开始。研究的第三阶段和最后阶段将在研究第17天开始，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天返回住院的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24小时以上。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，以确保瑞舒伐他汀不会影响其代谢；(2)在每次研究访问时，我们将绘制血脂板，以确定当瑞舒伐他汀与洛匹那韦/利托那韦联合使用时，是否对瑞舒伐他汀的降胆固醇能力有临床影响。最后，安全实验室将在每次研究访问期间绘制，以尽量减少研究参与者的风险。在研究访问时将进行药片计数和口头和书面依从性评估，以确保志愿者遵守研究程序。

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.