Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis

被引:57
作者
Asin-Prieto, Eduardo [1 ,2 ]
Rodriguez-Gascon, Alicia [1 ,2 ]
Troconiz, Inaki F. [3 ]
Soraluce, Amaia [1 ,2 ]
Maynar, Javier [4 ]
Angel Sanchez-Izquierdo, Jose [5 ]
Isla, Arantxazu [1 ,2 ]
机构
[1] Univ Basque Country UPV EHU, Fac Pharm, Pharmacokinet Nanotechnol & Gene Therapy Grp, Vitoria 01006, Spain
[2] Univ Basque Country UPV EHU, Ctr Invest Lascaray Ikergunea, Vitoria 01006, Spain
[3] Univ Navarra, Fac Pharm, Dept Pharm & Pharmaceut Technol, E-31080 Pamplona, Spain
[4] Univ Hosp Alava Sede Santiago, Intens Care Unit, Vitoria, Spain
[5] Doce de Octubre Hosp, Intens Care Unit, Madrid, Spain
关键词
antimicrobial therapy; beta-lactams; PD; PK; population pharmacokinetics; renal replacement therapy; intensive care; CONTINUOUS VENOVENOUS HEMOFILTRATION; NONLINEAR PHARMACOKINETICS; ANTIBACTERIAL AGENTS; CONTINUOUS-INFUSION; HEALTHY-VOLUNTEERS; CYSTIC-FIBROSIS; PHARMACODYNAMICS; FAILURE; ELIMINATION; INFECTIONS;
D O I
10.1093/jac/dkt304
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objectives: To evaluate the pharmacokinetics of piperacillin/tazobactam in critically ill patients undergoing continuous renal replacement therapy (CRRT) and to assess the success of the therapy against susceptible bacteria. Patients and methods: Sixteen patients undergoing CRRT with different degrees of renal function were included in the study. Blood and ultrafiltrate samples were drawn after administration of piperacillin/tazobactam (4/0.5 g) every 4, 6 or 8 h. The data were analysed by a population approach using NONMEM 7.2. The probability of target attainment (PTA) of maintaining free piperacillin levels above the MIC during the entire dosing interval was estimated by simulation of intermittent and continuous infusions. Results: The pharmacokinetics of piperacillin and tazobactam were best described by two-compartment models where the elimination of both drugs was conditioned by renal [dependent on creatinine clearance (CLCR)], non-renal and extracorporeal clearances. A 20 min infusion of piperacillin/tazobactam administered every 6 h provided high PTAs against MICs <= 32 mg/L in patients with severe renal failure. In patients with normal or moderate renal function PTAs >= 90% were only obtained up to MICs <= 8 mg/Lwith short infusions. However, simulating continuous infusion, higher probabilities of success were obtained against MICs of 32 and 16 mg/L when CLCR was 50 and 100 mL/min, respectively. Conclusions: Population pharmacokinetic models have been developed and validated for piperacillin and tazobactam. Based on the pharmacokinetic/pharmacodynamic analysis, dosing recommendations are given considering the residual renal function of the patient and the MIC for the isolated bacteria.
引用
收藏
页码:180 / 189
页数:10
相关论文
共 30 条
[1]   Elimination of piperacillin and tazobactam by renal replacement therapies with AN69 and polysulfone hemofilters:: Evaluation of the sieving coefficient [J].
Arzuaga, A. ;
Isla, A. ;
Gascon, A. R. ;
Maynar, J. ;
Corral, E. ;
Pedraz, J. L. .
BLOOD PURIFICATION, 2006, 24 (04) :347-354
[2]   Quantitation and stability of piperacillin and tazobactam in plasma and ultrafiltrate from patients undergoing continuous venovenous hemofiltration by HPLC [J].
Arzuaga, A ;
Isla, A ;
Gascón, AR ;
Maynar, J ;
Martín, A ;
Solinís, MA ;
Toral, D ;
Pedraz, JL .
BIOMEDICAL CHROMATOGRAPHY, 2005, 19 (08) :570-578
[3]   Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous Venovenous Hemofiltration [J].
Arzuaga, A ;
Maynar, J ;
Gascón, AR ;
Isla, A ;
Corral, E ;
Fonseca, F ;
Sánchez-Izquierdo, JA ;
Rello, J ;
Canut, A ;
Pedraz, JL .
JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 45 (02) :168-176
[4]   Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT [J].
Bauer, Seth R. ;
Salem, Charbel ;
Connor, Michael J. ;
Groszek, Joseph ;
Taylor, Maria E. ;
Wei, Peilin ;
Tolwani, Ashita J. ;
Fissell, William H. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 7 (03) :452-457
[5]   Prediction-Corrected Visual Predictive Checks for Diagnosing Nonlinear Mixed-Effects Models [J].
Bergstrand, Martin ;
Hooker, Andrew C. ;
Wallin, Johan E. ;
Karlsson, Mats O. .
AAPS JOURNAL, 2011, 13 (02) :143-151
[6]   Systematic comparison of the population pharmacokinetics and pharmacodynamics of piperacillin in cystic fibrosis patients and healthy volunteers [J].
Bulitta, J. B. ;
Dufful, S. B. ;
Kinzig-Schippers, M. ;
Holzgrabe, U. ;
Stephan, U. ;
Drusano, G. L. ;
Soergel, F. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (07) :2497-2507
[7]   Nonlinear pharmacokinetics of piperacillin in healthy volunteers - implications for optimal dosage regimens [J].
Bulitta, Juergen B. ;
Kinzig, Martina ;
Jakob, Verena ;
Holzgrabe, Ulrike ;
Soergel, Fritz ;
Holford, Nicholas H. G. .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2010, 70 (05) :682-693
[8]  
Clinical and Laboratory Standards Institute, 2012, M100S22 CLSI
[9]   PREDICTION OF CREATININE CLEARANCE FROM SERUM CREATININE [J].
COCKCROFT, DW ;
GAULT, MH .
NEPHRON, 1976, 16 (01) :31-41
[10]   Population Pharmacokinetics of Extended-Infusion Piperacillin-Tazobactam in Hospitalized Patients with Nosocomial Infections [J].
Felton, T. W. ;
Hope, W. W. ;
Lomaestro, B. M. ;
Butterfield, J. M. ;
Kwa, A. L. ;
Drusano, G. L. ;
Lodise, T. P. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (08) :4087-4094