Alcohol Inhibits Drug Metabolism by Carboxylesterases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Robbie Parker, University of Tennessee
ClinicalTrials.gov Identifier:
NCT01708369
First received: October 13, 2012
Last updated: October 15, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to determine if alcohol is able the affect the body's ability to eliminate two commonly used medication, oseltamivir and aspirin. We hypothesize that drinking alcohol may reduce the body's ability to break down these two medications along with many others.This could affect the amount of drug in the blood which could impact how well these drugs work and whether patients have side effects.


Condition Intervention Phase
Drug Interactions
Drug: Placebo
Drug: Ethanol
Drug: Oseltamivir
Drug: Aspirin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Inhibition of Carboxylesterase Metabolism by Ethanol

Resource links provided by NLM:


Further study details as provided by University of Tennessee:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve [ Time Frame: Oseltamivir 0-24 hrs; Aspirin 0-8 hours ] [ Designated as safety issue: No ]
    For determining if ethanol inhibits hCE1 or hCE2, the primary pharmacokinetic parameter of interest will be the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) for oseltamivir phosphate and acetylsalicylic acid, respectively. Other pharmacokinetic parameters that will be characterized are maximum plasma concentration (Cmax), time to reach the maximum plasma concentration (tmax), and the elimination rate constant λz. This same pharmacokinetic analysis will also be applied to the oseltamivir carboxylate and salicylic acid metabolites. The change in the metabolite formation clearance (∆Clf) for each agent will be calculated as the ratio of the metabolite to parent AUC0-∞ when given with ethanol (inh) and alone (con) as follows: ΔClf = [AUCm/AUCp]inh/[AUCm/AUCp]con


Enrollment: 19
Study Start Date: February 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Oseltamivir & Placebo
Oseltamivir 150 mg orally will be administered 15 minutes after subjects consume orange juice
Drug: Placebo
Orange juice administered 15 minutes before subjects take oseltamivir or aspirin
Other Name: Tropicana orange juice
Drug: Oseltamivir
Oseltamivir 150 mg orally
Other Name: Tamiflu
Experimental: Oseltamivir & Ethanol
Oseltamivir 150 mg and ethanol targeted to blood alcohol concentration 0.08 g/dl
Drug: Ethanol
Ethanol will be mixed with orange juice and subjects will drink the mixture 15 minutes before receiving oseltamivir or aspirin
Other Name: Ethanol plus Tropicana orange juice
Drug: Oseltamivir
Oseltamivir 150 mg orally
Other Name: Tamiflu
Active Comparator: Aspirin & Placebo
Aspirin 650 mg orally will be administered 15 minutes after subjects consume orange juice
Drug: Placebo
Orange juice administered 15 minutes before subjects take oseltamivir or aspirin
Other Name: Tropicana orange juice
Drug: Aspirin
Aspirin 650 mg orally will be given
Experimental: Aspirin & Ethanol
Aspirin 650 mg and ethanol targeted to blood alcohol concentration 0.08 g/dl
Drug: Ethanol
Ethanol will be mixed with orange juice and subjects will drink the mixture 15 minutes before receiving oseltamivir or aspirin
Other Name: Ethanol plus Tropicana orange juice
Drug: Aspirin
Aspirin 650 mg orally will be given

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers ages 21-45 with no chronic medical or psychiatric conditions
  • social ethanol drinker

Exclusion Criteria:

  • allergy or hypersensitivity to oseltamivir or aspirin
  • concomitant medication treatment (either prescription, over the counter, herbals, or supplements such as vitamins
  • co-existing diseases affecting cardiovascular, hepatic, renal, pulmonary, hematologic, or gastrointestinal function
  • platelet count < 100,000, hematocrit < 30
  • chronic psychiatric disorder
  • score >2 on the Michigan Alcohol Screening Test (MAST)
  • naive to alcohol ingestion, have a family history of alcohol dependence, or history of adverse responses to alcohol
  • women with known pregnancy, lactation, or not using and effective method of birth control (subjects taking oral contraceptives will be excluded)
  • ingestion of alcohol or caffeine during the study
  • participation in another drug study or blood donation within the preceding weeks.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01708369

Locations
United States, Tennessee
University of Tennessee Health Science Center
Memphis, Tennessee, United States, 38163
Sponsors and Collaborators
University of Tennessee
Investigators
Principal Investigator: Robert B Parker, PharmD University of Tennessee Health Science Center
Principal Investigator: Steven C Laizure, PharmD University of Tennessee Health Science Center
  More Information

No publications provided

Responsible Party: Robbie Parker, Professor, University of Tennessee
ClinicalTrials.gov Identifier: NCT01708369     History of Changes
Other Study ID Numbers: R15GM096074
Study First Received: October 13, 2012
Last Updated: October 15, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: Federal Government

Keywords provided by University of Tennessee:
human carboxylesterase-1
human carboxylesterase-2
alcohol
pharmacokinetics

Additional relevant MeSH terms:
Ethanol
Oseltamivir
Aspirin
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Antiviral Agents

ClinicalTrials.gov processed this record on September 18, 2014