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

Kennon Heard35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

Conditions

Drug Induced Liver Injury

Interventions

acetaminophenDRUG

Eligibility

Sex: ALLMin age: 21 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. age 21 years or older 2. provide written informed consent 3. consume, on average, less than 1 alcoholic beverage daily for the previous 3 months and would be considered non-drinkers Exclusion Criteria: 1. History of ingesting more than 4 grams of acetaminophen per day for any of the 4 days preceding study enrollment 2. Currently taking isoniazid 3. Consumption of any alcoholic beverage during the run-in period 4. A detectable serum acetaminophen at baseline 5. 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 6. Platelet count less than 125,000/cc at baseline 7. Positive pregnancy test at baseline (female participants only) 8. Currently adheres to a fasting type diet as determined by self report 9. Currently has anorexia nervosa as determined by self report 10. Subject appears clinically intoxicated, psychiatrically impaired or unable to give informed consent for any reason 11. Known hypersensitivity to acetaminophen

Outcomes

Primary Outcomes

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.

Time frame: Day 0, 4, 7, 9, 11, and 14.

Secondary Outcomes

Alanine Aminotransferase (ALT)

ALT was measured at Day 0, 4, 7, 9, 11, and 14.