title: Population pharmacokinetic analysis of piperacillin in burn patients.
abstract: Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CLCR), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CLCR/132] + DAI × [-0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CLCR. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CLCR of ≥ 160 ml/min.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Sangil
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Taegon
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jeongki
authors.initials: J
authors.lastname: Paek
authors.affiliation: Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University Medical Center, Gyeonggi-do, South Korea infwoo@hallym.or.kr yimds@catholic.ac.kr.
authors.forename: Heungjeong
authors.initials: H
authors.lastname: Woo
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea infwoo@hallym.or.kr yimds@catholic.ac.kr.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Yim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000209:etiology / Q000382:microbiology; D002056:Burns / Q000150:complications / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015233:Models, Statistical; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
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