Influence of Renal Function on the Pharmacokinetics of Piperacillin/Tazobactam in Intensive Care Unit Patients During Continuous Venovenous Hemofiltration

• Published in: Journal of clinical pharmacology 2005-02, Vol.45 (2), p.168-176
• Main Authors: Arzuaga, Alazne, Maynar, Javier, Gascón, Alicia R., Isla, Arantxazu, Corral, Esther, Fonseca, Fernando, Sánchez-Izquierdo, José Ángel, Rello, Jordi, Canut, Andrés, Pedraz, José Luis
• Format: Article
• Language: English
• Subjects: Aged; appropriate antimicrobial therapy; Area Under Curve; Blood; Chromatography, High Pressure Liquid - methods; Complications and side effects; continuous venovenous hemofiltration (CVVH); Critical Care; Dosage and administration; Drug therapy; Drug Therapy, Combination; Female; Filtration; Half-Life; Hemofiltration - methods; Humans; Inpatients; Intensive Care Units; Kidney - drug effects; Kidney - physiology; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - physiopathology; Male; Microbial Sensitivity Tests - methods; Middle Aged; Penicillanic Acid - administration & dosage; Penicillanic Acid - analogs & derivatives; Penicillanic Acid - blood; Penicillanic Acid - pharmacokinetics; peritonitis; pharmacokinetics; Piperacillin; Piperacillin - administration & dosage; Piperacillin - blood; Piperacillin - pharmacokinetics; Sepsis; tazobactam; Time Factors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270004269796

The pharmacokinetics of piperacillin/tazobactam (4 g/0.5 g every 6 or 8 hours, by 20‐minute intravenous infusion) were studied in 14 patients with acute renal failure who underwent continuous venovenous hemofiltration with AN69 membranes. Patients were grouped according to severity (CLCR 10 mL/min, 10 < CLCR 50 mL/min, and CLCR > 50 mL/min). A noncompartmental analysis was performed. The sieving coefficient (0.78 ± 0.28) was similar to the unbound fraction (0.65 ± 0.24) for tazobactam, but it was significantly different (0.34 ± 0.25) from the unbound fraction (0.78 ± 0.14) for piperacillin. Extracorporeal clearance was 37.0% ± 28.8%, 12.7% ± 12.6%, and 2.8% ± 3.2% for piperacillin in each group and 62.5% ± 44.9%, 35.4% ± 17.0%, and 13.1% ± 8.0% for tazobactam. No patients presented tazobactam accumulation. In patients with CLCR < 50 mL/min, tss(%) > MIC90 values were 100% for a panel of 19 pathogens, but in those with CLCR > 50 mL/min, tss(%) > MIC90 indexes were 55.5% and 16.6% for pathogens with MIC90 values of 32 and 64. The extracorporeal clearance of piperacillin/tazobactam is clinically significant in patients with CLCR > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.