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Using imipenem and cilastatin during continuous renal replacement therapy.
Alison Cotton1, Bryony Dean Franklin, Stephen Brett
1Pharmacy Department, Hammersmith Hospital NHS Trust, Du Cane Road, London W12 0HS, UK. acotton@hhnt.nhs.uk
Pharmacy World & Science : PWS
|December 13, 2005
Summary
This review found wide variations in pharmacokinetic studies of imipenem and cilastatin during continuous renal replacement therapy (CRRT). Further research is needed for reliable dosing recommendations in patients with renal and liver dysfunction.
Area of Science:
- Pharmacology
- Nephrology
- Critical Care Medicine
Background:
- Continuous renal replacement therapy (CRRT) is crucial for managing acute kidney injury in critically ill patients.
- Understanding drug pharmacokinetics, like imipenem and cilastatin, is vital for effective treatment during CRRT.
- Existing studies on imipenem/cilastatin pharmacokinetics during CRRT exhibit significant heterogeneity.
Purpose of the Study:
- To systematically review and synthesize existing literature on the pharmacokinetics of imipenem and cilastatin in patients undergoing CRRT.
- To identify gaps in current knowledge regarding drug dosing in this patient population.
Main Methods:
- A comprehensive literature search was conducted using databases such as Pharmline, Embase, and Medline.
- Search terms included "imipenem," "haemofiltration," "haemodialysis," and "pharmacokinetics."
- Studies focusing solely on intermittent haemodialysis were excluded to focus on continuous therapies.
Main Results:
- Seven studies detailing imipenem pharmacokinetics during CRRT were identified, utilizing four different CRRT modalities.
- Significant variability was observed in sampling methods, dosages, and pharmacokinetic calculation assumptions across studies.
- Reported total body clearance for imipenem ranged from 89 to 149 ml/min in acute renal failure, while cilastatin clearance ranged from 9 to 32 ml/min.
- Reduced clearance for both drugs was noted in chronic renal failure, and for cilastatin with impaired liver function.
- Dose recommendations varied widely, from 500 mg every 6 hours to 500 mg every 12 hours.
Conclusions:
- The heterogeneity among the reviewed studies precludes a unified analysis for definitive dosage recommendations.
- Further high-quality research involving larger patient cohorts is necessary.
- Future studies should provide more detailed information on liver dysfunction and the duration of renal failure to inform precise dosing strategies for imipenem and cilastatin during CRRT.