Drug-Drug Interaction Study With Pravastatin and Cyclosporine

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will address the following question: Does cyclosporine affect the pharmacokinetics of pravastatin in healthy volunteers? Studies have shown that cyclosporine inhibits the organic anion transporter required for pravastatin transport into the liver, thus increasing pravastatin levels in the blood. The investigators hypothesize that this inhibition will vary among people based on genetic differences. This knowledge is important to help develop safer and more effective drug therapy with reduced side effects.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: National Institute of General Medical Sciences (NIGMS)
• Treatments: Cyclosporine; Cyclosporins; Pravastatin

Criteria

Inclusion Criteria:

• Carrier of one of the three SLCO1B1 polymorphisms that we are studying (SLCO1B1 521TT, 521TC, 521CC)

• Men or women (women must have negative pregnancy test)

• ages 18 to 45 years

• Caucasian

• Healthy, including no renal or hepatic disease, as determined from plasma creatinine and liver enzyme levels

• No medications currently, except for vitamins and oral contraceptive pills

• Willingness to spend two nights at the San Francisco General Hospital

• Sign informed consent

Exclusion Criteria:

• Under 18 years old

• Unable to confirm Caucasian ancestry

• Pregnant or lactating women (female subjects will have a urine pregnancy test at the screening visit)

• Prior history of allergic reaction to pravastatin or cyclosporine

• Has a risk of congestive heart failure requiring pharmacologic treatment (medical history)

• Has prior renal or hepatic dysfunction

• Risk of urinary or gastric retention or narrow-angle glaucoma (by medical history examination)

• Impaired renal function (e.g. as suggested by abnormal creatinine clearance, eGFR < 60 or serum creatinine > 1.4 mg/dl in females and > 1.5 mg/dl in males) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction (heart attack), and septicemia, abnormal heart rhythms (tachyarrhythmias; heart beat > 100 beats per minute)

• Impaired hepatic function (> 1.5 times the upper limit of normal)

• Evidence of anemia (hemoglobin <10g)

• Taking medications other than vitamins that could confound study results

• They do not provide informed consent to participate in the study