Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients
The study hypothesis is to measure how the drug doripenem is cleared from the body of critically ill trauma patients. The investigators will measure blood drug concentrations and calculate how much the drug distributes in the body and how fast it is removed from the body. There is little information on how drugs are cleared in critically ill patients and the wrong dose of a drug could make it ineffective. The investigators will use this information to predict the most reasonable dose to treat infections effectively in these patients.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients With Sepsis at Grady Health System|
- Volume of Distribution (Vd) [ Time Frame: After 3rd dose of study medication ] [ Designated as safety issue: No ]The Volume of distribution is the calculated volume that the given amount of drug is uniformly distributed in the body to achieve a particular concentration
- Clearance (CL) [ Time Frame: After 3rd dose of study medication ] [ Designated as safety issue: No ]Clearance is the volume of drug removed from the body per unit of time (hrs).
- Elimination Constant (ke) [ Time Frame: after 3rd dose of study drug ] [ Designated as safety issue: No ]The elimination rate constant of a drug from the central compartment
|Study Start Date:||April 2010|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Doripenem group
Patients will receive doripenem for the treatment of their infection
Doripenem 1 gm administered over 4 hours X 3 doses
Understanding the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of an antibiotic can provide insight into developing appropriate dosing regimens. It is even more imperative at the present time to maximize PK/PD parameters since there are no new novel antimicrobial agents to treat resistant gram-negative infections. This approach allows us to achieve superior PD parameters and treat bacteria that would have been resistant to standard dosing due to higher minimum inhibitory concentrations (MICs).
Doripenem exhibits time-dependent bactericidal activity and the pharmacodynamic parameter predicting clinical and bacteriologic outcomes is the percentage of the dosing interval that free drug concentrations remain above the minimum inhibitory concentration (T > MIC) of the infecting pathogen Sepsis is known to influence drug pharmacokinetics and pharmacodynamics as a result of changes in hemodynamics, capillary permeability, third spacing, acid-base status, serum proteins, and organ function. Moreover, trauma patients tend to be younger with fewer comorbidities. They are hypermetabolic and are often given aggressive fluid resuscitation resulting in increased renal clearance of drugs and a larger volume of distribution. As a consequence of these differences in PK parameters, the calculated PD parameters will likely differ resulting in sub-optimal T> MIC. For time-dependent antibacterial agents such as doripenem, the T > MIC is one of the most important pharmacodynamic parameters in predicting clinical efficacy, therefore it is imperative to evaluate the PK parameters in this particular population.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01027897
|United States, Georgia|
|Grady Memorial Hospital|
|Atlanta, Georgia, United States, 30303|
|Principal Investigator:||Jeffrey Salomone, MD||Emory University|