Pharmacokinetics (PK) of Ertapenem Intravenous (IV) Bolus Versus Standard Infusion

Study Overview
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Brief Summary
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The purpose of this study is to characterize and compare the concentration-time profiles and multiple dose pharmacokinetics of a 5 minute intravenous (IV) bolus of ertapenem 1 gram daily versus the standard 30 minute infusion in healthy volunteers. Safety and tolerability and pharmacodynamic target attainment using Monte Carlo simulation will also be assessed and compared.

Official Title
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Comparative Pharmacokinetics, Safety, and Pharmacodynamics of Ertapenem 1 Gram Daily Administered as an IV Bolus Versus Standard 30 Minute Infusion to Healthy Adult Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: ertapenem
* Drug: ertapenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults (18 years of age or older) Exclusion Criteria: Ertapenem or other beta-lactam allergy Pregnant or breast feeding females Body Mass Index (BMI) greater than or equal to 30 Abnormal lab values at baseline Hypertension Significant medical abnormality Regular alcohol consumption Significant nicotine use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ertapenem 1 gram intravenous (IV) 5 minute bolus<br>Participants received ertapenem 1 gram every 24 hours for 3 doses with each dose infused as a 5 minute IV bolus. | Drug: ertapenem<br>* 1 gram IV bolus every 24 hours (q24h) for 3 days<br>|
| Active Comparator: Ertapenem 1 gram IV 30 minute infusion<br>Participants received ertapenem 1 gram every 24 hours for 3 doses with each dose infused as a 30 minute infusion (i.e., the standard dose). | Drug: ertapenem<br>* 1 gram 30 minute infusion q24h for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) at Steady-State (After 3rd Dose) | Cmax is measured at 5 minutes after the beginning of the infusion for the 5 minute IV bolus dosage regimen and at 30 minutes after the beginning of the infusion for the 30 minute infusion dosage regimen. | 5 or 30 minutes post start of infusion on Day 3 | 
| Area Under the Curve From 48 to 72 Hours [AUC(48-72)] | AUC(48-72) is the 24 hour area under the concentration versus time curve after the 3rd dose of ertapenem, which is selected to measure approximate AUC at steady-state. | 0-24 hours after 3rd ertapenem dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | The following laboratory assessments will be make before and after participation in the study to determine if objective changes occurred: blood pressure, pulse rate, temperature, complete blood count with differential, platelet count, blood urea nitrogen, serum creatinine, liver function panel [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase], total bilirubin, and urinalysis with microscopy. Monitoring of other pathologic or unintended changes in structure (signs),or function (symptoms) of the body associated with participation in the study will occur. | 3 days | 
| Probability of Target Attainment (PTA) | After simulating 5000 patients receiving each dosing regimen, the probability of achieving free drug concentrations above an MIC of 0.25 mcg/mL and 0.5mcg/mL for at least 40% of the dosing interval (40% fT>MIC) is calculated at each MIC dilution. | Simulated Steady-State Exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Safety