Pharmacokinetic Study of Paracetamol in Patients Over 80 Years Hospitalized to an Acute Geriatric Ward

The goal of this exploratory study is the characterization of the pharmacokinetic (PK) profile of paracetamol in older patients and the specific PK (pharmacokinetic) variables associated with plasma exposure in this population.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Procedure: Venopuncture for PK profiling

Detailed Description

The goal of this exploratory study is the characterization of the pharmacokinetic profile of paracetamol in older patients and the specific PK variables associated with plasma exposure in this population. The primary endpoint is the identification of the pharmacokinetic parameters: area under the curve (AUC), peak plasma concentration after administration of paracetamol (Cmax) and the time at which the Cmax is observed (Tmax) of paracetamol. The secondary endpoint consists of 3 sub-endpoints:

1. The variability in plasma exposure: volume of distribution (Vd), clearance (Cl) and elimination half-life (t1/2)
2. The association between the PK parameters and pathophysiological factors
3. The correlation between PK parameters and clinical parameters.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• a minimum age of 80 years
• admission to the acute geriatrics ward
• oral intake of paracetamol 1000 milligram (mg) in tablet form tid
• a steady state situation (defined as at least 4 consecutive intakes of paracetamol before sampling)

Exclusion Criteria:

• palliative care setting with downgrading of care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paracetamol oral tablets 1g tid; Patients received paracetamol one gram three times daily. Venopuncture for PK profiling	Procedure: Venopuncture for PK profiling; Blood samples at T0, T0.5, T1, T2, T4, T6; Other Names: Blood sampling for paracetamol dosage
Experimental: Paracetamol oral granules 1g tid; Patients received paracetamol one gram three times daily. Venopuncture for PK profiling	Procedure: Venopuncture for PK profiling; Blood samples at T0, T0.5, T1, T2, T4, T6; Other Names: Blood sampling for paracetamol dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the pharmacokinetic parameters: AUC	Area under the curve (AUC)	8 hours (= during 1 dosing interval at steady state)
Identification of the pharmacokinetic parameters: Cmax	Peak plasma concentration after administration of paracetamol (Cmax)	8 hours (= during 1 dosing interval at steady state)
Identification of the pharmacokinetic parameters: Tmax	The time at which the Cmax is observed (Tmax) of paracetamol	8 hours (= during 1 dosing interval at steady state)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in plasma exposure: Vd	Volume of distribution (Vd)	8 hours (= during 1 dosing interval at steady state)
Variability in plasma exposure: t1/2	Elimination half-life (t1/2)	8 hours (= during 1 dosing interval at steady state)
Variability in plasma exposure: Cl	Clearance (Cl)	8 hours (= during 1 dosing interval at steady state)
The association between the AUC (area under the curve) of paracetamol and patient related factors.	Multivariate analysis will be performed with AUC (area under the curve) as outcome. This will allow to identify variables influencing AUC of paracetamol. Patient related factors include amongst others age, weight, albumin, bilirubin, serum creatinin and co medication.	8 hours (= during 1 dosing interval at steady state)
The association between the AUC (area under the curve) of paracetamol and pain scores.	Pain scores will be based on the Numeric Rating Scale with a score of 0 indicating no pain and a score of 10 indicating worst imaginable pain.	8 hours (= during 1 dosing interval at steady state)
Correlation between immuno assay method and the Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine paracetamol concentrations in serum	Correlation between two different assays will be determined through Bland Altman statistics.	8 hours (= during 1 dosing interval at steady state)

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Isabel Spriet, PharmD PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: November 29, 2016
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: S58396 - mp05485

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No