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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Pain

Intervention / Treatment
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* Procedure: Venopuncture for PK profiling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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) |