Drug-Drug Interaction Study With Pravastatin and Cyclosporine
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Screening Procedures:

      Prior to enrollment, subjects will be asked to come to the Clinical and Translational Science
      (CTSI) Clinical Research Center (CRC) at San Francisco General Hospital (SFGH). The study
      protocol and procedures will be explained in detail, all questions will be answered, and
      subjects will be provided with a consent form to sign. The screening visit will be conducted
      within 14 days of the first inpatient visit (i.e. first pravastatin with placebo or
      pravastatin with cyclosporine dosing day)

      Only after subjects have consented to participate in the study will the screening procedures
      commence. During the screening visit, vital signs as well as blood sample (10 mL) will be
      taken by venipuncture to measure a complete blood count (CBC), electrolytes, blood urea
      nitrogen (BUN), creatinine, and liver function tests (LFTs) to screen for anemia and renal or
      hepatic insufficiency (see Inclusion/Exclusion Criteria)

      Procedures During Main Study:

      An equal number of subjects will be randomized, by a computer program, into one of the two
      study arms described below. On the first day of the study, subjects will be dosed with either
      100 mg cyclosporine or placebo at 8PM, followed by an overnight fast. On the morning of Day
      2, subjects will be asked to take a second dose of 100 mg cyclosporine or placebo at 8AM. At
      9AM of Day 2, subjects will be asked to take 40 mg pravastatin. Plasma samples (5 ml) will be
      collected at baseline (prior to pravastatin administration), then at 0.25, 0.5, 0.75, 1, 1.5,
      2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 hours post-dose. Whole blood will also be collected 12 hours
      post-dose to measure the cyclosporine level.

      The procedures during the second visit of the study will be identical to the first, but with
      dosing of 100 mg cyclosporine or placebo, opposite of what was dosed at the first study
      visit.

      Clinical and Laboratory Determinations:

      Analytical Methods:

      Measurement of pravastatin in plasma will be performed by High Performance Liquid
      Chromatography (HPLC) with tandem mass spectrometry (MS/MS), using assays previously
      described and validated.
    

Intervention name(s): Pravastatin alone; Pravastatin and Cyclosporine
Intervention type(s): Drug; Drug
Intervention description(s): Pravastatin 40 mg with placebo.; Pravastatin 40 mg co-administered with 200 mg of cyclosporine.
Intervention MeSH terms: Cyclosporine; Pravastatin; Cyclosporins
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science