Pharmacokinetics of meropenem in patients with various degrees of renal function, including patients with end-stage renal disease

Abstract

The pharmacokinetics of meropenem were studied after intravenous infusion in 13 patients grouped according to the impairment of their renal function. Creatinine clearance (CLCR) was greater than 50, 50 to 30, and less than 30 ml/min in groups I, II, and III, respectively. Two other groups, groups IV and V, each comprising four patients with end-stage renal disease (CLCR, < 5 ml/min), were also studied, the former on days off of hemodialysis and the latter on days of hemodialysis. The elimination half-lives of meropenem were 1.54 +/- 0.70 h in group I patients, 3.36 +/- 1.02 h in group II patients, and 5.00 +/- 1.05 h in group III patients. Cumulative urinary excretion accounted for 48.5% of the dose in group I patients and decreased progressively with a decline in renal function. Hemodialysis shortened the elimination half-life of meropenem from 7.0 h to 2.9 h. H-4295, the main metabolite of meropenem, had a peak level in plasma of 0.5 to 1.0 h in patients with renal failure. The level of H-4295 decreased with hemodialysis. The dosing interval of meropenem should be prolonged in a regular proportion to the decline in CLCR (12 h in group II patients and 24 h in group III patients). In patients receiving hemodialysis, dosing after each hemodialysis session is recommended.

An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis

“…administrations, respectively. This is slightly below values previously described for patients with end-stage renal disease without renal replacement therapy (11).…”

Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration

“…Emerging retrospective human data suggest that clinical advantages may exist for maintaining meropenem concentrations for longer periods and at concentrations up to five times the MIC (f 100% TϾ 5ϫMIC ) (1,17). While the elimination half-life of meropenem is increased in patients with renal dysfunction, the addition of RRT will cause some level of meropenem clearance (6,9,14,23,26). Therefore, dosing strategies specific for critically ill patients receiving RRT are essential to optimize antibiotic exposure and minimize the poor clinical outcomes observed in these patients (19).…”

Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae

“…The temperature of the central compartment was maintained at 37°C with constant stirring to ensure homogeneous mixing and instantaneous distribution. A peristaltic pump (Masterflex L/S; Cole-Parmer, Vernon Hills, IL), with a flow rate of 1.56 ml/min to simulate a half-life (t 1/2 ) of 2 h for rifampin and meropenem, was used to deliver CAMHB into the central compartment with displacement of an equal volume (43,47). Polymyxin B was administered as a constant infusion of 0.5, 1, or 2 mg/liter into the central compartment throughout the experiment (area under the concentration-time curve to 24 h [AUC 24 ] of 12, 24, or 48 mg · h/liter), thereby simulating the unbound average steady-state concentrations (C ss ) and flat concentration-time profiles seen in critically ill patients (40,41,48).…”