Drug biotransformation interactions in man VI: acetaminophen and ascorbic acid

Area of Science:

• Pharmacology
• Drug Metabolism
• Biochemistry

Background:

• Acetaminophen is a common analgesic.
• Acetaminophen is metabolized in the liver via glucuronidation and sulfation.
• Sulfate conjugation is a significant metabolic pathway for acetaminophen.

Purpose of the Study:

• To investigate the effect of ascorbic acid on acetaminophen metabolism and excretion.
• To determine if ascorbic acid influences the sulfation pathway of acetaminophen.
• To assess changes in acetaminophen's biological half-life when co-administered with ascorbic acid.

Main Methods:

• Five healthy adult volunteers received an oral dose of acetaminophen.
• Ascorbic acid was administered orally 1.5 hours after acetaminophen.
• Urine samples were analyzed to quantify acetaminophen and its metabolites (sulfate, glucuronide).
• Sodium sulfate was co-administered in a separate trial to assess its effect.

Main Results:

• Ascorbic acid administration led to a rapid decrease in acetaminophen sulfate excretion.
• The fraction of acetaminophen excreted as glucuronide and unchanged drug increased.
• The biological half-life of acetaminophen significantly increased from 2.3 to 3.1 hours.
• Co-administration of sodium sulfate prevented these metabolic alterations.

Conclusions:

• Ascorbic acid inhibits acetaminophen sulfation, likely by competing for available sulfate.
• This competition leads to altered acetaminophen metabolic profiles and an increased half-life.
• Understanding these interactions is crucial for drug safety and efficacy, especially concerning vitamin C supplementation.