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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00935363
Recruitment Status : Withdrawn
First Posted : July 9, 2009
Last Update Posted : January 14, 2015
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: glyburide Drug: glyburide + fluconazole Drug: glyburide + rifampin Drug: glyburide + fluconazole + rifampin Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Study Start Date : February 2010
Estimated Primary Completion Date : March 2010
Estimated Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: glyburide + fluconazole Drug: glyburide + fluconazole
single dose oral glyburide single dose iv fluconazole

Experimental: glyburide + rifampin Drug: glyburide + rifampin
single dose oral glyburide single dose iv rifampin

Active Comparator: glyburide Drug: glyburide
single oral dose

Experimental: glyburide + fluconazole + rifampin Drug: glyburide + fluconazole + rifampin
single dose oral glyburide single dose iv fluconazole single dose iv rifampin

Primary Outcome Measures :
  1. Drug Plasma Levels [ Time Frame: 24 hours ]

Secondary Outcome Measures :
  1. Blood sugar levels [ Time Frame: 24 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Responsible Party: University of California, San Francisco Identifier: NCT00935363     History of Changes
Other Study ID Numbers: GlyburideOATP2C9
First Posted: July 9, 2009    Key Record Dates
Last Update Posted: January 14, 2015
Last Verified: January 2015

Keywords provided by University of California, San Francisco:
drug interaction
Healthy Volunteers

Additional relevant MeSH terms:
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Hypoglycemic Agents