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Interplay Between Organic Anion Transporting Polypeptide (OATP) Transporters Transporters and CYP2C9 in Glyburide Pharmacokinetics (PK)

Registration Number
NCT00935363
Lead Sponsor
University of California, San Francisco
Brief Summary

The purpose of this study is to investigate if the drugs rifampin and fluconazole when given together increase the concentrations in the body of the oral diabetes medication glyburide.

Detailed Description

The purpose of this study is to find out if a drug interaction occurs when glyburide is taken with rifampin and fluconazole. Glyburide is an oral drug commonly used to lower blood glucose levels in diabetic patients. Rifampin is an antibiotic used to treat tuberculosis and a variety of other infections caused by certain germs called bacteria. Both drugs affect a protein found in your liver cells called organic anion transporting polypeptides (OATPs). This protein regulates drugs getting into and out of your body. Fluconazole is commonly used to treat fungal infections like candidiasis, urinary tract infections and a variety of other infections caused by fungi. It interacts with glyburide by affecting your body's ability to breakdown glyburide. Since both rifampin and fluconazole play a role in the way glyburide enters and remains active in the body, we want to find out what effect taking the three drugs together has on the level of glyburide in the blood.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on history, physical exam and laboratory evaluations;
  • BMI between 18.5 - 30 kg/m2;
  • Taking no medications 2 weeks before and during the study enrollment, including drugs of abuse, prescription or OTC medications (except acetaminophen);
  • Subjects must be able to maintain adequate birth control during the study independent of hormonal contraceptive use;
  • Be able to provide written informed consent and comply with requirements of the study;
  • Avoid eating grapefruit and drinking grapefruit juice from 7 days before the first study day until completion of the entire study;
  • Abstinence from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of that study day;
  • Fast from food and beverages at least 8 hours prior to medication dosing;
  • Be able to read, speak and understand English
Exclusion Criteria
  • Subjects on prescription or chronic over-the counter medications (including hormonal contraceptives);
  • Subjects with known allergy to glyburide and/or rifampin and/or fluconazole;
  • Subjects who are not homozygous for CYP2C9 *1 (known poor metabolizers);
  • Subjects with liver failure or LFTs >2x upper limit of normal;
  • Subjects with clinically significant elevations in SCr, BUN or other screening laboratory tests as determined by study physician;
  • Subjects with Hct <30 mg/dL;
  • Subjects who smoke tobacco;
  • Subjects with ongoing alcohol or illegal drug use;
  • Subjects who are pregnant, lactating or attempting to conceive;
  • Subjects unable to maintain adequate birth control during the study;
  • Subjects unable to follow protocol instructions or protocol criteria.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
glyburide + fluconazoleglyburide + fluconazole-
glyburide + fluconazole + rifampinglyburide + fluconazole + rifampin-
glyburide + rifampinglyburide + rifampin-
glyburideglyburide-
Primary Outcome Measures
NameTimeMethod
Drug Plasma Levels24 hours
Secondary Outcome Measures
NameTimeMethod
Blood sugar levels24 hours
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