NCT01246713

Effect on Acetaminophen Metabolism by Liquid Formulations

Effect on Acetaminophen Metabolism by Liquid Formulations: Do Excipients in Liquid Formulation Prevent Production of Toxic Metabolites?

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Beth Israel Deaconess Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine whether excipients in the liquid formulation of acetaminophen prevent the formation of the toxic metabolites of acetaminophen.

Detailed description

Acetaminophen (APAP) poisoning is the most frequent cause of acute hepatic failure in the United States. Toxicity requires cytochrome P-450 bioactivation of APAP. Children are less susceptible to APAP toxicity; the current theory is that they have different metabolism than adults. However, children's liquid preparations of APAP contain excipients which have been shown to inhibit APAP bioactivation in vitro and in rodents. Children tend to ingest liquid preparations, which could potentially explain their decreased susceptibility instead of an intrinsically different metabolism. Further, our review of Poison Center epidemiologic data shows that liquid preparations are less toxic in adults. Our hypothesis is that excipients in liquid preparations inhibit the bioactivation of APAP. The design is a pharmacokinetic cross-over study in humans. Healthy adult subjects will be recruited for administration of therapeutic doses of APAP in capsule and liquid formulations. Plasma via a heplock will be collected at serial time points up to 8 hours and assayed for APAP and its metabolites. After a washout period, subjects will receive the same dose of APAP in the alternate preparation. The pattern of metabolites, indicating the activity of the bioactivating enzymes, will be compared. A significant difference in P-450 metabolites will support the hypothesis and provide preliminary data for studies in patients who have ingested potentially toxic doses of APAP. Ultimately, this work could support development of novel antidotal therapy for APAP overdose.

Conditions

• Acetaminophen Metabolism
• Acetaminophen Poisoning
• Drug Metabolism by Excipients

Interventions

Type	Name	Description
DRUG	Acetaminophen liquid formulation	Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.
DRUG	Acetaminophen solid formulation	Subjects in this arm will receive a 15mg/kg dose of a solid acetaminophen formulation.

Timeline

• Start date: 2010-12-01
• Primary completion: 2011-05-01
• Completion: 2012-07-01
• First posted: 2010-11-23
• Last updated: 2017-05-08
• Results posted: 2013-05-08

Locations

1 site across 1 country: United States