Pharmacokinetics of Meropenem in Patients with Renal Failure and Patients Receiving Renal Replacement Therapy

Abstract

Meropenem is a well established carbapenem antibacterial with a wide spectrum of activity against Gram-positive and Gram-negative bacteria, including β-lactamase producers and Pseudomonas aeruginosa. Because of its clinical and bacteriological efficacy, meropenem is an important antimicrobial drug in the treatment of serious infections in adults and in children. Meropenem is predominately excreted unchanged in the urine, and thus dosage adjustments are necessary in patients with renal insufficiency and those undergoing intermittent haemodialysis (IHD) or various forms of continuous renal replacement therapy (CRRT), such as continuous venovenous haemodialysis, continuous venovenous haemodiafiltration (CVVHDF), continuous venovenous haemofiltration (CVVHF) or continuous ambulatory peritoneal dialysis (CAPD). The half-life of meropenem (approximately 1 hour in healthy volunteers) is prolonged up to 13.7 hours in anuric patients with end-stage renal disease. In patients receiving renal replacement therapy, half-life is influenced by drug-specific factors as well by membrane and treatment modalities (IHD, CRRT or CAPD). Plasma meropenem concentrations reach a peak of between 53 and 62 mg/L after the administration of meropenem 1g intravenously to healthy volunteers, up to 53 mg/L after meropenem 0.5g in haemodialysis patients, and between 18 and 45 mg/L after meropenem 1g during CRRT in critically ill patients. Approximately 50% of meropenem is eliminated by IHD, 25 to 50% by CVVHF and 13 to 53% by CVVHDF. Such differences are not negligible and demonstrate the great influence of the treatment modality on the elimination of the drug during renal replacement therapy. Thus, physicians run the risk of underdosing with this antimicrobial drug because of the quite different recommendations in the literature. Because of the excellent tolerability profile of meropenem, such underadministration should be avoided.