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 (CVVHF). Design: Prospective, open-labeled study. Setting: Medical intensive care unit of the University Medical Center Utrecht. Patients: Five critically ill patients receiving CVVHF for acute renal failure treated with meropenem for documented or suspected bacterial infection. Intervention: All patients received meropenem (500 mg) administered intravenously every 12 hrs. Plasma samples and ultrafiltrate aliquots were collected during one dosing interval. Measurements and 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 CVVHF 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. Conclusion: In critically ill patients with acute renal failure, nonrenal clearance became the main elimination route. CVVHF 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 CVVHF, according to our operational characteristics. This dosing regimen resulted in adequate trough plasma levels for susceptible microorganisms.