The Effects of Rifampin on the Pharmacokinetics of Rosuvastatin

Study Overview
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Brief Summary
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The effect of transporter inhibition by rifampin on the pharmacokinetics of rosuvastatin will be studied in clinical trial in White and Asian healthy volunteers.

Official Title
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The Effects of Single-Dose Rifampin on the Pharmacokinetics of Rosuvastatin in Healthy White and Asian Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Rosuvastatin plus rifampin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Asian volunteers of Han-Chinese/Japanese/Korean descent whose parents and grandparents are Han-Chinese/ Japanese/ Korean. Healthy Caucasian volunteers of White/Caucasian/European-born descent whose parents and grandparents are White/Caucasian/European. Male or female, ages 18-65 years old, with no current medical conditions or active diagnoses as determined by the study doctor based on history, physical exam, and laboratory evaluations. Subjects who take no other medications two weeks prior to the study and during the time course of the study including prescription medications, over-the-counter medications, dietary supplements, or drugs of abuse. Subjects with the following genotype: SLCO1B1*1a and ABCG2 421CC. Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use. Subjects able to abstain from grapefruit, grapefruit juice, oranges, orange juice, caffeinated beverages and/or alcoholic beverages from 7am the day before the study to completion of that study day. Participants determined to have normal liver and kidney function as measured at baseline BMI between 18.0 - 30 kg/m2 Subjects capable of fasting from food and beverages at least 8 hours prior to medication dosing. Be able to read, speak, and understand English. Subjects capable of providing informed consent and completing the requirements of the study. Exclusion Criteria: Subjects with active medical problems Subjects on chronic prescription or OTC medication that cannot be stopped 2 weeks prior to and during the study. 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 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 rifampin or any known component of the medications Anyone who in the opinion of the study investigators is unable to do the study

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rosuvastatin<br> | Drug: Rosuvastatin<br>* Rosuvastatin 20mg po x1<br>* Other names: Crestor;|
| Experimental: Rifampin plus rosuvastatin<br> | Drug: Rosuvastatin plus rifampin<br>* Rifampin 600mg IV infused over 30 minutes followed by rosuvastatin 20mg PO x1<br>* Other names: Rifampicin;|

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 |  | Blood samples collected over a 48 hour period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of rosuvastatin |  | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 32, and 48 hours post-dose | 
| Time to concentration maximum (Tmax) of rosuvastatin |  | 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 32, and 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rosuvastatin, rifampin, pharmacokinetics, drug interaction, healthy volunteer, drug transporter, Asian, White