Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery Clinical Trial
— RSTOfficial title:
Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients
| Verified date | January 2020 |
| Source | University of California, San Francisco |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 21 |
| Est. completion date | December 6, 2018 |
| Est. primary completion date | December 6, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Taiwan | E-Da Hospital | Kaohsiung | |
| United States | University of California, San Francisco | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| University of California, San Francisco | E-DA Hospital |
United States, Taiwan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Area-under-the-concentration curve (AUC) of rosuvastatin | 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing | ||
| Secondary | 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. | |
| Secondary | 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 |