Paracetamol Metabolism After Liver Surgery

Liver Resection Clinical Trial

— PETALS  

Official title:

Observational Study Assessing Cytochrome P450 Dependant Paracetamol Metabolites Following Liver Resection.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01770041
• Other study ID #: 12/SS/0222
• Status: Completed
• Phase: N/A
• First received: January 15, 2013
• Last updated: October 15, 2014
• Start date: February 2013
• Est. completion date: June 2014

Study information

• Verified date: October 2014
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

This observational study will assess the metabolic pathways of paracetamol that are utilised after liver resection.

Description:

Paracetamol is normally metabolised by the glucuronidation and sulfation of paracetamol to non toxic end products. If paracetamol is administered in supra-therapeutic doses this pathway becomes saturated and an alternative pathway is utilised. This results in a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). If NAPQI is not metabolised by glutathione to cysteine and mercapturic acid, then NAPQI bind to hepatic cells resulting in necrosis and hepatotoxicity.

Therefore the investigators plan to measure the levels of the paracetamol metabolites in patient undergoing liver resection.

Patients will undergo liver resection according to their onco-surgical requirements. As part of the normal post operative care they will receive 1g paracetamol every six hours unless stated otherwise by the operating surgeon. Urinary samples will be taken for the first 4 post operative days and used for analysis of the urinary paracetamol metabolite levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients undergoing liver surgery

Exclusion Criteria:

• Contra-indication to paracetamol

• Inability to give written, informed consent.

• Jaundice (Bilirubin > 100 µmol/L).

• Liver resection combined with secondary surgical procedure.

• Age < 18 years.

• Pregnant women.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Liver Resection
• Paracetamol Administration

Intervention

Other:
• Paracetamol (observation of routine administration)
Normal administration of paracetamol as prescribed by operating surgeon

Locations

Country	Name	City	State
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh	Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glucuronamide		Post-operative days 1-4	No
Other	Sulphate		Post-operative days 1-4	No
Other	5-oxoproline		Post-operative days 1-4	No
Other	Complications		Day of surgery and post-operative days 1-30	No
Other	Post-operative blood tests (FBC, U&E, LFTs, Coag)		Post-operative dyas 1-7	No
Primary	Urinary cysteine		Post operative days 1-4	No
Secondary	mercapturic acid		post operative days 1-4	No
Secondary	Glutathione		day of surgery and post operative days 1 and 3	No
Secondary	Paracetamol level		day of surgery and post operative days 1 and 3	No