Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients

被引:36
|
作者
Chung, Eun Kyoung [1 ]
Cheatham, S. Christian [2 ]
Fleming, Megan R. [3 ]
Healy, Daniel P. [4 ]
Shea, Katherine M. [5 ]
Kays, Michael B. [6 ]
机构
[1] Kyung Hee Univ, Coll Pharm, Seoul, South Korea
[2] Franciscan St Francis Hlth, Dept Pharm, Indianapolis, IN USA
[3] Methodist Dallas Med Ctr, Dept Pharm, Dallas, TX USA
[4] Univ Cincinnati, Acad Hlth Ctr, Div Pharm Practice & Adm Sci, James L Winkle Coll Pharm, Cincinnati, OH USA
[5] Univ Med Ctr Brackenridge, Dept Pharm, Seton Healthcare Family, Austin, TX USA
[6] Purdue Univ, Coll Pharm, Indianapolis, IN USA
来源
JOURNAL OF CLINICAL PHARMACOLOGY | 2015年 / 55卷 / 08期
关键词
piperacillin; tazobactam; obesity; NONMEM; Monte Carlo simulation; NONLINEAR PHARMACOKINETICS; CRITICALLY-ILL; ANTIBIOTICS; COMBINATION; SOCIETY; ADULTS;
D O I
10.1002/jcph.505
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients. Twenty-seven patients (total body weight [TBW], 60 to 211kg; body mass index [BMI], 19.6 to 72.9kg/m(2)) received 4.5 or 6.75g every 8 hours, infused over 4 hours, and serum concentrations were measured at steady state. Population pharmacokinetic parameters were estimated using NONMEM, and Monte Carlo simulations were performed for three 4-hour dosing regimens to calculate probability of target attainment (PTA) at 50% fT>MIC.A 1-compartment linear-elimination model best fit the pharmacokinetic data for piperacillin and tazobactam. Creatinine clearance (CRCL), TBW, and BMI were significantly associated with piperacillin pharmacokinetics, and CRCL was significantly associated with tazobactam pharmacokinetics. Clearance and volume of distribution for piperacillin and tazobactam were significantly different between obese and nonobese patients (P < .05). At MICs 16mg/L, PTA was >90% for dosing regimens 3.375g every 8 hours in nonobese patients and 4.5g every 8 hours in obese patients. Piperacillin and tazobactam pharmacokinetics are altered in obesity, and 4.5g every 8 hours infused over 4 hours should be recommended for empiric therapy in obese patients.
引用
收藏
页码:899 / 908
页数:10
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