Pharmacokinetics of Meropenem in Patients with Renal Failure and Patients Receiving Renal Replacement Therapy
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Clin Pharmacokinet 2000 Oct; 39 (4): 271-279 0312-5963/00/0010-0271/$20.00/0 © Adis International Limited. All rights reserved.
Pharmacokinetics of Meropenem in Patients with Renal Failure and Patients Receiving Renal Replacement Therapy Florian Thalhammer1 and Walter H. Hörl2 1 Department of Internal Medicine I, Division of Infectious Diseases, and Institute of Virology, University of Vienna, Vienna, Austria 2 Department of Internal Medicine III, Division of Nephrology and Dialysis, University of Vienna, Vienna, Austria
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Pharmacodynamic Relationships . . . . . . . . . . . . . . . . . 2. Pharmacokinetics in Patients with Renal Failure . . . . . . . . . 3. Pharmacokinetics in Patients on Renal Replacement Therapy 3.1 Intermittent Haemodialysis . . . . . . . . . . . . . . . . . . 3.2 Continuous Renal Replacement Therapy . . . . . . . . . . 3.3 Continuous Ambulatory Peritoneal Dialysis . . . . . . . . . 4. Comparison of Meropenem with Imipenem/Cilastatin . . . . . 5. Dosage Recommendations . . . . . . . . . . . . . . . . . . . . 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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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
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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
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