Pharmacokinetics (PK) of Ertapenem Intravenous (IV) Bolus Versus Standard Infusion
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
|Official Title:||Comparative Pharmacokinetics, Safety, and Pharmacodynamics of Ertapenem 1 Gram Daily Administered as an IV Bolus Versus Standard 30 Minute Infusion to Healthy Adult Volunteers|
- Maximum Observed Plasma Concentration (Cmax) at Steady-State (After 3rd Dose) [ Time Frame: 5 or 30 minutes post start of infusion on Day 3 ] [ Designated as safety issue: No ]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.
- Area Under the Curve From 48 to 72 Hours [AUC(48-72)] [ Time Frame: 0-24 hours after 3rd ertapenem dose ] [ Designated as safety issue: No ]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.
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]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.
- Probability of Target Attainment (PTA) [ Time Frame: Simulated Steady-State Exposure ] [ Designated as safety issue: No ]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.
|Study Start Date:||August 2010|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: Ertapenem 1 gram intravenous (IV) 5 minute bolus
Participants received ertapenem 1 gram every 24 hours for 3 doses with each dose infused as a 5 minute IV bolus.
1 gram IV bolus every 24 hours (q24h) for 3 days
Active Comparator: Ertapenem 1 gram IV 30 minute infusion
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).
1 gram 30 minute infusion q24h for 3 days
|United States, Connecticut|
|Hartford, Connecticut, United States, 06102|
|Principal Investigator:||Josepth L Kuti, PharmD||Hartford Hospital|
|Study Director:||Dora E Wiskirchen, PharmD||Hartford Hospital|