Using imipenem and cilastatin during continuous renal replacement therapy.
OBJECTIVE
To identify and review studies which have sought to define the pharmacokinetics of imipenem and cilastatin in patients receiving continuous renal replacement therapy (CRRT).


METHODS
Literature was primarily identified using Pharmline, Embase and Medline databases using the search terms "imipenem," "haemofiltration," "haemodialysis" and "pharmacokinetics." Papers that discussed only intermittent haemodialysis were excluded.


RESULTS
Seven papers were identified which described the pharmacokinetics of imipenem in patients receiving CRRT. Four different modes of CRRT were used. The methods of sampling, dosages used and assumptions made during pharmacokinetic calculations varied widely between the studies. Total body clearance of imipenem during CRRT in patients suffering from acute renal failure was found to range between 89 and 149 ml/min. Total body clearance of cilastatin ranged between 9 and 32 ml/min. Total body clearance of both imipenem and cilastatin was reduced in patients with chronic renal failure. Total body clearance of cilastatin was also reduced by impaired liver function. Dose recommendations made ranged between 500 mg 6-hourly and 500 mg 12-hourly.


CONCLUSIONS
The heterogeneity of the studies identified prevents them being analysed as a single group. For meaningful dosage recommendations to be made, further studies are required using larger populations and with more detail regarding liver dysfunction and duration of renal failure.
Cotton
Alison
A
Pharmacy Department, Hammersmith Hospital NHS Trust, Du Cane Road, London W12 0HS, UK. acotton@hhnt.nhs.uk
Franklin
Bryony Dean
BD
Brett
Stephen
S
Holmes
Alison
A
D058186:Acute Kidney Injury / Q000378:metabolism / Q000628:therapy*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006440:Hemofiltration / Q000379:methods; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D011480:Protease Inhibitors; D015377:Cilastatin; D015378:Imipenem