EVAL OF PHRMACOKIN INTERACTIONS BETWEEN CRESTOR&COMBO PROTEASE INHIBITOR KALETRA

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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.