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

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.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: glyburide + fluconazole; Drug: glyburide + rifampin; Drug: glyburide; Drug: glyburide + fluconazole + 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.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Drug Plasma Levels	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood sugar levels	24 hours

Collaborators and Investigators

• Sponsor: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Anticipated): March 1, 2010
• Study Completion (Anticipated): April 1, 2010

Study Registration Dates

• First Submitted: July 7, 2009
• First Submitted That Met QC Criteria: July 8, 2009
• First Posted (Estimate): July 9, 2009

Study Record Updates

• Last Update Posted (Estimate): January 14, 2015
• Last Update Submitted That Met QC Criteria: January 12, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: pharmacokinetics; Healthy Volunteers; pharmacodynamics; drug interaction; glyburide
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Rifampin; Fluconazole; Glyburide
• Other Study ID Numbers: GlyburideOATP2C9