Population pharmacokinetics of meropenem in burn patients

被引:50
作者
Doh, Kichan [1 ]
Woo, Heungjeong [2 ]
Hur, Jun [3 ]
Yim, Haejun [3 ]
Kim, Jimyon [1 ]
Chae, Hongseok [1 ]
Han, Seunghoon [1 ]
Yim, Dong-Seok [1 ]
机构
[1] Catholic Univ Korea, Coll Med, Dept Pharmacol, Seoul 137701, South Korea
[2] Hallym Univ, Med Ctr, Hangang Sacred Heart Hosp, Dept Internal Med, Seoul 150710, South Korea
[3] Hallym Univ, Med Ctr, Hangang Sacred Heart Hosp, Dept Burn Surg & Burn Ctr, Seoul 150710, South Korea
关键词
PK-PD modelling; Monte Carlo simulation; NONMEM; resistance; DOSAGE; CEFTAZIDIME; GENTAMICIN;
D O I
10.1093/jac/dkq317
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
To develop a population pharmacokinetic model of meropenem in burn patients and to explore the appropriateness of current dosage regimens. Fifty-nine patients with burns ranging from 3% to 97% of total body surface area treated with meropenem were analysed. The population pharmacokinetic parameters of meropenem in 59 burn patients were estimated, and concentrations were simulated by using a mixed effect method (NONMEM, ver. 6.2). The final model was a two-compartment model with first-order elimination where creatinine clearance (CLCR) and oedema contributed. The mean population pharmacokinetic parameters were clearance (L/h) = 4.45 + 10.5 x CLCR (mL/min)/138, V1 (central volume) = 17.0 + 11.1 x presence of oedema (0 or 1) L, V2 (peripheral volume) = 10.1 L and Q (intercompartmental clearance) = 5.25 L/h with interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated), respectively. The population clearance and volume of distribution in our burn patients were significantly greater than those reported in non-burn patients. The simulation of 1000 virtual patients' plasma meropenem concentration treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted the probability of achieving the time above MIC > 40% of the dosing interval as 58.9% for Pseudomonas aeruginosa isolated from three university hospitals in Korea.
引用
收藏
页码:2428 / 2435
页数:8
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