Pharmacokinetics and dosing regimen of meropenem in critically ill patients receiving continuous venovenous hemofiltration.
OBJECTIVE
To study the pharmacokinetics of meropenem in critically ill patients with acute renal failure receiving continuous venovenous hemofiltration (CWHF).


METHODS
Prospective, open-labeled study.


METHODS
Medical intensive care unit of the University Medical Center Utrecht.


METHODS
Five critically ill patients receiving CWHF for acute renal failure treated with meropenem for documented or suspected bacterial infection.


METHODS
All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval.


RESULTS
Mean age and body weight of the patients studied were 46.6 yrs (range, 28-61 yrs) and 85.8 kg (range, 70-100 kg), respectively. The following pharmacokinetic variables for meropenem were obtained: mean peak plasma concentration was 24.5 +/- 7.2 mg/L, mean trough plasma concentration was 3.0 +/- 0.9 mg/L, mean terminal elimination half-life was 6.37 +/- 1.96 hrs, mean total plasma clearance was 4.57 +/- 0.89 L/hr, mean CWHF clearance was 1.03 +/- 0.42 L/hr, mean nonrenal clearance was 3.54 +/- 1.06 L/hr, and mean volume of distribution was 0.37 +/- 0.15 L/kg.


CONCLUSIONS
In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CWHF substantially contributed to the clearance of meropenem (23% of mean total plasma clearance). We recommend meropenem to be dosed at 500 mg intravenously every 12 hrs in patients receiving CWHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.
Ververs
T F
TF
Division of Hospital Pharmacy, University Medical Center Utrecht, The Netherlands.
van Dijk
A
A
Vinks
S A
SA
Blankestijn
P J
PJ
Savelkoul
J F
JF
Meulenbelt
J
J
Boereboom
F T
FT
D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism* / Q000628:therapy*; D000328:Adult; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D016638:Critical Illness; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007262:Infusions, Intravenous; D016018:Least-Squares Analysis; D008297:Male; D000077731:Meropenem; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
D013845:Thienamycins; D000077731:Meropenem