Alcohol Inhibits Drug Metabolism by Carboxylesterases

NCT01708369 | Completed Phase 1

• 1 other identifier: R15GM096074
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug Interactions

Keywords

human carboxylesterase-1; human carboxylesterase-2; alcohol; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Area under the plasma concentration-time curve

  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

  Oseltamivir 0-24 hrs; Aspirin 0-8 hours

Study Arms (4)

Oseltamivir & Placebo

ACTIVE COMPARATOR

Oseltamivir 150 mg orally will be administered 15 minutes after subjects consume orange juice

Drug: Placebo; Drug: Oseltamivir

Oseltamivir & Ethanol

EXPERIMENTAL

Oseltamivir 150 mg and ethanol targeted to blood alcohol concentration 0.08 g/dl

Drug: Ethanol; Drug: Oseltamivir

Aspirin & Placebo

ACTIVE COMPARATOR

Aspirin 650 mg orally will be administered 15 minutes after subjects consume orange juice

Drug: Placebo; Drug: Aspirin

Aspirin & Ethanol

EXPERIMENTAL

Aspirin 650 mg and ethanol targeted to blood alcohol concentration 0.08 g/dl

Drug: Ethanol; Drug: Aspirin

Interventions

Placebo DRUG

Orange juice administered 15 minutes before subjects take oseltamivir or aspirin

Also known as: Tropicana orange juice

Aspirin & Placebo; Oseltamivir & Placebo

Ethanol DRUG

Ethanol will be mixed with orange juice and subjects will drink the mixture 15 minutes before receiving oseltamivir or aspirin

Also known as: Ethanol plus Tropicana orange juice

Aspirin & Ethanol; Oseltamivir & Ethanol

Oseltamivir DRUG

Oseltamivir 150 mg orally

Also known as: Tamiflu

Oseltamivir & Ethanol; Oseltamivir & Placebo

Aspirin DRUG

Aspirin 650 mg orally will be given

Aspirin & Ethanol; Aspirin & Placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Tennessee: lead

Study Sites (1)

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

MeSH Terms

Interventions

Ethanol; Oseltamivir; Aspirin

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Acetamides; Amides; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic

Study Officials

• Robert B Parker, PharmD

  University of Tennessee

  PRINCIPAL INVESTIGATOR

• Steven C Laizure, PharmD

  University of Tennessee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 13, 2012
• First Posted: October 16, 2012
• Study Start: February 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: October 16, 2012

Record last verified: 2012-10

Locations

US (1)