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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00935363
First received: July 7, 2009
Last updated: February 22, 2011
Last verified: July 2009
  Purpose

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 Intervention
Healthy
Drug: glyburide
Drug: glyburide + fluconazole
Drug: glyburide + rifampin
Drug: glyburide + fluconazole + rifampin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Drug Plasma Levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood sugar levels [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: February 2010
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Leslie Z. Benet, Ph.D., University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00935363     History of Changes
Other Study ID Numbers: GlyburideOATP2C9
Study First Received: July 7, 2009
Last Updated: February 22, 2011
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Glyburide
Fluconazole
Rifampin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014