Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous venovenous hemofiltration.
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 (CL(CR) < or =10 mL/min, 10 < CL(CR) < or =50 mL/min, and CL(CR) > 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 CL(CR) < 50 mL/min, t(%)ss >MIC90 values were 100% for a panel of 19 pathogens, but in those with CL(CR) > 50 mL/min, t(%)ss >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 CL(CR) > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.
Arzuaga
Alazne
A
Laboratorio de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Paseo de la Universidad no. 7, 01006 Vitoria-Gasteiz, Spain.
Maynar
Javier
J
Gascón
Alicia R
AR
Isla
Arantxazu
A
Corral
Esther
E
Fonseca
Fernando
F
Sánchez-Izquierdo
José Angel
JA
Rello
Jordi
J
Canut
Andrés
A
Pedraz
José Luis
JL
D000368:Aged; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003422:Critical Care; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D007297:Inpatients; D007362:Intensive Care Units; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000078142:Tazobactam; D013997:Time Factors
D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin