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Doripenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy
Mahesh N Samtani1, Nicole Vaccaro, Iolanda Cirillo
1Clinical Pharmacology, Janssen Research & Development, L.L.C., 920 Route 202, Raritan, NJ 08869, USA.
ISRN Pharmacology
|August 14, 2012
Summary
Doripenem doses need reduction in critically ill patients undergoing continuous venovenous hemofiltration (CVVH) or hemodiafiltration (CVVHDF). New dosing recommendations ensure efficacy while minimizing exposure risks in these patient populations.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Critical Care Medicine
- Infectious Diseases
Background:
- Doripenem is a broad-spectrum antibiotic.
- Continuous renal replacement therapies (CRRT) like CVVH and CVVHDF alter drug pharmacokinetics.
- Optimizing antibiotic dosing in CRRT is crucial for patient outcomes.
Purpose of the Study:
- To establish appropriate doripenem dosing regimens for patients on CVVH and CVVHDF.
- To ensure therapeutic efficacy (fT > MIC) and avoid excessive drug exposure.
- To meet regulatory requirements for updated product information.
Main Methods:
- Pharmacokinetic/pharmacodynamic (PK/PD) simulations were used.
- Efficacy target: free doripenem concentrations above MIC (1 mg/L) for ≥35% of the dosing interval.
- Simulations incorporated 40% intersubject variability and doubled nonrenal clearance.
Main Results:
- Doripenem dose reduction is necessary for patients receiving CVVH or CVVHDF.
- Simulated regimens achieved ≥90% probability of meeting the efficacy criterion.
- Exposure was maintained below levels seen with high-dose regimens in healthy subjects.
Conclusions:
- Revised doripenem dosing is recommended for critically ill patients on CRRT.
- Updated dosing recommendations have been added to the Doribax Summary of Product Characteristics.
- This study provides evidence-based guidance for antibiotic use in a vulnerable patient group.
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