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Comparative Effects of Azithromycin, Telithromycin and Levofloxacin on Drug Metabolizing Enzymes

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: NCT00164112
Recruitment Status : Completed
First Posted : September 14, 2005
Last Update Posted : September 14, 2005
PriCara, Unit of Ortho-McNeil, Inc.
Information provided by:
Bassett Healthcare

Brief Summary:
Studies have previously shown that a broad drug interaction screening can be performed using enzyme specific probes such as oral caffeine for CYP1A2, N-acetyltrasferase-2 (NAT-2), and xanthine oxidase (XO), warfarin plus vitamin K for CYP2C9, omeprazole for CYP 2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4/5. This combination of probes has been validated in the Cooperstown 5+1 Cocktail (5+1).1 The use of the 5+1 cocktail provides information on the drug metabolizing enzymes that metabolize 90% of hepatically eliminated drugs for a fraction of the costs of the individual studies. Using a cocktail of biomarkers reduces the overall cost of drug interaction screening. The purpose of this study is to evaluate the effects of three Food and Drug Administration (FDA) approved oral antibiotics (azithromycin, telithromycin, and levofloxacin) on metabolism of other medications when taken together. This will be determined by the measuring the activity of drug metabolizing enzymes following administration of certain drug probes (caffeine, dextromethorphan, omeprazole, midazolam, and warfarin with vitamin K). A total of 16 subjects will complete four phases of the study: 1) Cooperstown 5+1 alone, 2) Azithromycin plus Cooperstown 5+1, 3) Telithromycin plus Cooperstown 5+1, and 4) Levofloxacin plus Cooperstown 5+1.

Condition or disease Intervention/treatment Phase
Healthy Drug: Cooperstown 5+1 alone Drug: Azithromycin plus Cooperstown 5+1 Drug: Telithromycin plus Cooperstown 5+1 Drug: Levofloxacin plus Cooperstown 5+1 Phase 4

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Study Type : Interventional  (Clinical Trial)
Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Comparison of the Effect of Azithromycin, Telithromycin and Levofloxacin on Drug Metabolizing Enzymes Using the Validated Cooperstown 5+1 Cocktail
Study Start Date : November 2004
Study Completion Date : June 2005

Primary Outcome Measures :
  1. Phenotype measures

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy adults between the ages of 18 and 55 years.
  • Ability to provide written informed consent.
  • Willing to avoid all medications (other than the study drugs) which may inhibit or induce hepatic microsomal enzymes during the study period. This includes prescription and non-prescription medications, vitamins, herbal supplements, and nutriceuticals.
  • Willing to avoid drinking more than the equivalence of one beer per day (one 12 ounce beer or equivalent alcohol intake) throughout the study period.
  • Women of child-bearing potential who are willing to practice non-hormonal methods of contraception during all study phases.
  • Willing to adhere to dietary restrictions as required during the study.

Exclusion Criteria:

  • Clinically significant abnormal findings by history, physical exam, ECG, or laboratory testing.
  • Elevated liver function tests twice above the upper limit of the normal range (males AST 0-50 U/L, ALT 0-60 U/L, GGT 11-50; females AST 0-40 U/L, ALT 0-50 U/L, GGT 7-32), or total bilirubin >1.3mg/dL.
  • Baseline INR >1.2.
  • Serum creatinine above the normal ranges
  • Women who are pregnant, breastfeeding, and/or not using an acceptable form of non-hormonal contraception (barrier method or abstinence) during the study.
  • History of gastrointestinal bleeding or peptic ulcer disease.
  • Any condition that may affect drug absorption (e.g., gastrectomy, malabsorption syndromes).
  • History of known hypersensitivity or serious adverse reaction to azithromycin, telithromycin, levofloxacin, midazolam, dextromethorphan, caffeine, omeprazole, heparin, warfarin, or vitamin K.
  • Poor IV access as determined by an investigator.
  • Current illicit drug use.
  • History of tobacco use within 3 months of screening.
  • Use of any drug known to inhibit or induce hepatic enzymes within 30 days of the first study phase.
  • Regular alcohol intake exceeding 1 drink/day (1 drink = 5 ounces of wine or 12 ounces of beer or 1 ounce of hard liquor) within 1 months of screening.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study drug.
  • Presence of any condition that the investigator feels would interfere with successful completion of the study.
  • Poor metabolizers of CYP2D6, CYP2C9, and CYP2C19.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00164112

Sponsors and Collaborators
Bassett Healthcare
PriCara, Unit of Ortho-McNeil, Inc.
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Principal Investigator: Joseph S Bertino, Pharm.D. Bassett Healthcare
Layout table for additonal information Identifier: NCT00164112    
Other Study ID Numbers: CAPSS-273
First Posted: September 14, 2005    Key Record Dates
Last Update Posted: September 14, 2005
Last Verified: March 2005
Keywords provided by Bassett Healthcare:
Cooperstown Cocktail
Drug Metabolizing Enzymes
Drug Interactions
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors