title: Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients.
abstract: 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 211 kg; body mass index [BMI], 19.6 to 72.9 kg/m(2) ) received 4.5 or 6.75 g 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 ≤ 16 mg/L, PTA was >90% for dosing regimens ≥3.375 g every 8 hours in nonobese patients and ≥ 4.5 g every 8 hours in obese patients. Piperacillin and tazobactam pharmacokinetics are altered in obesity, and 4.5 g every 8 hours infused over 4 hours should be recommended for empiric therapy in obese patients.
authors.affiliation: College of Pharmacy, Kyung Hee University, Seoul, South Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Chung
authors.affiliation: Franciscan St. Francis Health, Department of Pharmacy, Indianapolis, IN, USA.
authors.forename: S Christian
authors.initials: SC
authors.lastname: Cheatham
authors.affiliation: Methodist Dallas Medical Center, Department of Pharmacy, Dallas, TX, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Fleming
authors.affiliation: James L. Winkle College of Pharmacy, Division of Pharmacy Practice and Administrative Sciences, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.affiliation: Seton Healthcare Family, University Medical Center at Brackenridge, Department of Pharmacy, Austin, TX, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Shea
authors.affiliation: Purdue University College of Pharmacy, Indianapolis, IN, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015992:Body Mass Index; D001835:Body Weight; D003198:Computer Simulation; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D009765:Obesity / Q000378:metabolism*; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D010397:Penicillanic Acid; D003404:Creatinine; D000078142:Tazobactam; D010878:Piperacillin
keywords: Monte Carlo simulation; NONMEM; obesity; piperacillin; tazobactam