Acetaminophen Adduct Formation in Non-Drinkers Taking Therapeutic Doses of Acetaminophen for Ten Consecutive Days

Study Overview
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Brief Summary
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Acetaminophen is commonly used to treat fever or pain. Your body clears acetaminophen by processing it in the liver. During the processing, some of the acetaminophen may bind to proteins in the liver. The protein-acetaminophen product is called an adduct. After a large acetaminophen overdose, the liver has to process a lot of acetaminophen, so large amounts of adducts are formed. However, we have found that lower levels may be formed even when people take recommended doses. The purpose of this study is to measure the amount of adducts formed when healthy people who do not drink alcohol take normal doses of acetaminophen for 10 days.

Official Title
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Acetaminophen Adduct Formation in Alcohol Abstaining Subjects Administered Therapeutic Doses of Acetaminophen for Ten Consecutive Days

Conditions
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Drug Induced Liver Injury

Intervention / Treatment
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* Drug: acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 21 years or older provide written informed consent consume, on average, less than 1 alcoholic beverage daily for the previous 3 months and would be considered non-drinkers Exclusion Criteria: History of ingesting more than 4 grams of acetaminophen per day for any of the 4 days preceding study enrollment Currently taking isoniazid Consumption of any alcoholic beverage during the run-in period A detectable serum acetaminophen at baseline Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 50 IU/L at the start of the run-in period or at baseline Platelet count less than 125,000/cc at baseline Positive pregnancy test at baseline (female participants only) Currently adheres to a fasting type diet as determined by self report Currently has anorexia nervosa as determined by self report Subject appears clinically intoxicated, psychiatrically impaired or unable to give informed consent for any reason Known hypersensitivity to acetaminophen

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>all subjects receive 4 g/day of acetaminophen for 10 consecutive days in this open-label study | Drug: acetaminophen<br>* 4 g/day for 10 consecutive days<br>* Other names: Tylenol Extra Strength;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Level of Acetaminophen-cysteine (APAP-Cys) Protein Adducts | Acetaminophen-cysteine (APAP-Cys) protein adduct concentrations were measured at Day 0, 4, 7, 9, 11 and 14. All units are in nmol/mL serum. | Day 0, 4, 7, 9, 11, and 14. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine Aminotransferase (ALT) | ALT was measured at Day 0, 4, 7, 9, 11, and 14. | Day 0, 4, 7, 9, 11, and 14. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acetaminophen, protein adducts, hepatic function, drug safety, non drinkers