Single-Dose Pharmacokinetics of Meropenem during Continuous Venovenous Hemofiltration

Abstract

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 ± 18.6 ml/min and 2.46 ± 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 ± 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 ± 2.7 μg/ml, and trough levels after 6 h of CVVH were 6.6 ± 1.5 μg/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 ± 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis*

“…The dialysatebased estimates of dialysis clearance and the fraction removed for meropenem were too low in comparison with the dialysis clearance estimated from drug concentrations before and after application of the dialysis membrane. A possible explanation for this observation (already described previously) could be adsorption of meropenem by the dialysis membrane (25) or instability of meropenem in the dialysate.…”

How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

“…In these studies, CRRT caused more than 50% of meropenem CL total when a higher CRRT intensity was used (effluent flow rate N70 mL/min) (Bilgrami et al, 2010;Giles et al, 2000;Isla et al, 2005;Kielstein et al, 2006;Krueger et al, 1998Krueger et al, , 2003Langgartner et al, 2008;Robatel et al, 2003;Seyler et al, 2011;Tegeder et al, 1999;Thalhammer et al, 1998;Ververs et al, 2000). Substantial clearance of meropenem was also observed during PIRRT (Deshpande et al, 2010;Kielstein et al, 2006).…”

“…Variations in RRT settings, such as type of filter material, blood flow rate and effluent flow rate settings can result in changes to antibiotic pharmacokinetics, (Choi et al, 2004;Lam et al, 2010;Tegeder et al, 1999;Thalhammer et al, 1998). In general, when higher RRT intensities are used (i.e.…”

Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy

“…Studies of patients on CRRT receiving MEM have proposed doses ranging from 500 mg every 12 hours [42,43] to 1 g every 12 hours [20,44]. In nine septic patients, the V d was 29.5 ± 2.7 l ( V d = 39.7 l (14.8 to 184.7 l) in the present study), the AUC was 118.0 ± 15.8 mg/hour/l, the total CL was 143.7 ± 18.6 ml/minute (total CL = 88.7 ml/minute (43.2 to 205.7 ml/minute) in the present study) and the t 1/2 was 2.33 ± 0.38 hours [42]. On the basis of a literature review, Trotman and colleagues suggested doses of 1 g every 12 hours for CVVH or CVVHDF [16].…”