Rosuvastatin Interethnic PK Study

Study Overview
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Brief Summary
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Statins are the first-line and most commonly prescribed drugs for the prevention of cardiovascular diseases and stroke in the world. Our preliminary studies suggest that Caucasians might have a higher risk of developing potentially life-threatening drug-drug interactions than Asians when taking statins. Drug-drug interactions occur in the body when two or more drugs interact in a way that alters their effectiveness and/or toxicity. These interactions are becoming an increasingly severe problem with statin usage since patients at higher risk for cardiovascular diseases also take statins combined with many other drugs, such as antihypertensive and diabetic drugs. Our study is aimed at understanding the molecular factors and providing a sound basis for the interethnic dosage and response differences for statins. Drug-transporting proteins in intestine and liver tissues are responsible for taking up statins into the blood. It is hypothesized that there are interethnic function differences of these proteins and that they account for differences in statin blood levels between Caucasians and Asians and the frequency and/or severity of their respective drug-drug interactions. A clinical study will be conducted with Caucasian and Asian subjects undergoing gastric bypass surgery so excess intestine and liver tissue can be acquired as part of the standard procedure. Protein levels will be quantified in the tissues and correlate them with different statin blood levels.

Official Title
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Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients

Conditions
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Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery

Intervention / Treatment
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* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects that are scheduled for bariatric surgery. Subjects that are able and willing to donate surplus intestinal tissue. Subjects with solute carrier organic anion transporter *1 (SLCO1B1) and breast cancer resistant protein (BCRP) 421CC genotypes. White/Caucasian/European and Asian/East Asian heritage individuals, male or female, 18 years of age or older. BMI between 30-55 kg/m2 Be able to read, speak, and understand English(UCSF) and Chinese(Taiwan). Subjects capable of providing informed consent and completing the requirements of the study. Exclusion Criteria: Subjects with active liver and kidney problems, severe cardiovascular diseases, type I diabetes, advanced pulmonary disease, and cancers. Subjects on chronic prescription or over the counter medication that have previously been reported to exhibit drug-drug interactions with rosuvastatin and cannot be stopped two weeks prior to and during the study, including gemfibrozil, cyclosporine, atazanavir, lopinavir and ritonavir. Subjects incapable of multiple blood draws (HCT < 30mg/dL). Subjects with a history of rhabdomyolysis. Subjects with a history of drug-related myalgias. Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias. Subjects with a history of GI bleed or peptic ulcer disease. Subjects with a recent history of trauma. Subjects who smoke tobacco or have ongoing alcohol or illegal drug use. Subjects who are pregnant, lactating, or trying to conceive during the study period. Subjects allergic to rosuvastatin or any known component of the medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asians<br>Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor | Drug: Rosuvastatin<br>* Rosuvastatin 20mg po x1<br>* Other names: Crestor;|
| Experimental: Caucasians<br>Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor | Drug: Rosuvastatin<br>* Rosuvastatin 20mg po x1<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area-under-the-concentration curve (AUC) of rosuvastatin |  | 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in oral clearance of rosuvastatin | Changes in oral clearance of rosuvastatin within gastric bypass surgery will be analyzed using the ratio of areas under the systemic concentration curves (AUCs) from before to after surgery using the bioequivalence criteria of 80-125%. The oral clearance will be calculated based on the plasma data from each of the blood draws after the dosing period is completed (48hr). The pre and post surgery period are separated by at least a 8-week recovery period. | Pre-surgery period: 48 hr after dosing; post-surgery period: 48 hr after dosing. Two periods separated by at least two months. | 
| Descriptive comparison of messenger ribonucleic acid (mRNA) and protein expression in the tissues | Tissue samples will be collected on the day of the surgery. | Day of the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rosuvastatin, PK, Interethnic, Morbid obese