PK/PD of High Dose Pip/Tazo in Obese Patients

Study Overview
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Brief Summary
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Worldwide rates of obesity have doubled in the last 30 years, and obesity has been associated as a risk factor for hospital-acquired infections and increased occurrence of death in critically-ill patients. Piperacillin/tazobactam is a commonly prescribed antibiotic for critically ill patients with an infection, however, limited information exists for dosing this drug in obese patients. In these limited reports, standard doses of piperacillin/tazobactam given to the small number of obese patients resulted in lower blood concentrations, which could lead to inadequate killing of bacteria. The purpose of this study is to compare blood concentrations from standard piperacillin/tazobactam dosing compared to higher dosing regimens in obese patients. This study will also include information on the safety and tolerability of the higher dose regimens. The study investigators believe that the higher dosing regimen will produce adequate blood levels in obese patients and will not add any more risk of harm to obese patients receiving this higher dose.

Official Title
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Pharmacokinetics and Pharmacodynamics of High-Dose Piperacillin/Tazobactam in Obese Patients

Conditions
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Obesity

Intervention / Treatment
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* Drug: Piperacillin/Tazobactam Standard Dose to High Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI greater than or equal to 30 kg/m2 Weight at least 105 kg Age 18-89 years of age Prescribed piperacillin/tazobactam at standard doses for suspected or confirmed infection(s) English or Spanish speaking Central line access Exclusion Criteria: Do not meet specified inclusion criteria Hepatic impairment classified by Child-Pugh Class B or greater Documented pre-existing seizure disorder Documented pre-existing hematologic disorder Pregnancy Documented allergy or contraindication to beta-lactams or tazobactam

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Dose to High Dose Piperacillin/Tazobactam<br>Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Then, they will be switched to higher dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared. | Drug: Piperacillin/Tazobactam Standard Dose to High Dose<br>* Patients will receive a standard dose of piperacillin/tazobactam, then will have subsequent pharmacokinetic analyses on the blood concentrations drawn while on standard dose. Patients will be switched to higher dose after receiving the standard dose, with subsequent pharmacokinetic analyses performed on those blood concentrations while on higher dose. These pharmacokinetics of each dosing regimen will be compared.<br>* Other names: Zosyn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Maximum Concentrations for Piperacillin | Pharmacokinetic parameters for piperacillin of maximum serum concentration (Cmax) will be measured in both standard dosing and high dosing. | 0, 1, 3, and 6 hours post-dose | 
| Serum Minimum Concentrations of Piperacillin | Minimum serum concentrations (Cmin) of piperacillin will be measured in both standard and high doses | 0, 1, 3, and 6 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Half-life of Piperacillin | Half-life (t1/2) of piperacillin will be calculated from serum concentrations in both standard and high doses | 0, 1, 3, and 6 hours post-dose | 
| Volume of Distribution of Piperacillin | Volume of distribution (Vd) of piperacillin will be calculated from serum concentrations in both standard and high doses | 0, 1, 3, and 6 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, obesity, piperacillin-tazobactam combination product, pharmacodynamics, piperacillin/tazobactam