Sangil Jeon (1), Heungjeong Woo (2), Seunghoon Han (1), Jongtae Lee (1), Taegon Hong (1), Jeongki Paek (1), Hyeongsik Hwang (2), Dong-Seok Yim (1)
(1) Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, (2) Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea
Objectives: Piperacillin-tazobactam is a parenterally administered combination of β-lactam antibiotic/β-lactamase inhibitor. It shows broad antibacterial activity against Pseudomonas aeruginosa and other pathogens. This combination has been frequently used 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.
Methods: Fifty patients with burns ranging from 1% to 81% of total body surface area treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for about 30 minutes at a dose of 4.5 g every 8 h. Blood samples were collected right before and at 1, 2, 3, 4 and 6 h after more than 5 infusions. The population PK model of piperacillin was developed using a nonlinear mixed effect method (NONMEM, ver 7.2).
Results: The final model was a two-compartment model with first-order elimination. Covariates included in the final model were creatinine clearance (CLCR) on the clearance and sepsis on the central volume of piperacillin. The mean population PK parameters were; clearance (L/h) = 15 × CLCR (mL/min) / 132, V1 (central volume) = 24.6 + 16.3 × presence of sepsis L, V2 (peripheral volume) = 14.6 L, and Q (intercompartmental clearance) = 0.645 L/h with interindividual variability (CV%) of 36.0%, 38.3%, 0%(not estimated) and 93.7%, respectively.
Conclusions: The population PK of piperacillin have been characterized in burn patients after infusion. These results are to be used for further pharmacodynamic modeling and simulation in burn patients.
References:
[1] Dowell JA, Korth-Bradley J., Milisci M., Tantillo K., Amorusi P., Tse S. Evaluating possible pharmacokinetic interactions between tobramycin, piperacillin, and a combination of piperacillin and tazobactam in patients with various degrees of renal impairment. J Clin Pharmacol 2001, 41: 979-86.
[2] Roberts JA, Kirkpatrick CM, Roberts MS, Dalley AJ, Lipman J: First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents 2010, 35:156-163.
Reference: PAGE 22 (2013) Abstr 2816 [www.page-meeting.org/?abstract=2816]
Poster: Infection