title: Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients.
abstract: The study objective was to evaluate steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Fourteen hospitalised patients weighing >120kg received piperacillin/tazobactam 4.5 g every 8 h (q8h) or 6.75 g q8h infused over 4h. Blood samples were collected at steady-state and drug concentrations were determined. Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens. The probability of target attainment (PTA) for ≥50% fT>MIC was calculated for piperacillin at various MICs, and the PTA for fAUC(0-24)≥96 mg h/L was calculated for tazobactam. Mean±S.D. patient demographics were: age 49±10 years; weight 161±29 kg; and body mass index 52.3±10.8 kg/m(2). For piperacillin and tazobactam, respectively, the mean±S.D. elimination rate was 0.440±0.177 h(-1) and 0.320±0.145 h(-1), volume of distribution was 33.4±14.0L (0.21±0.07L/kg) and 37.5±15.3L (0.23±0.08 L/kg), and systemic clearance was 13.7±5.2L/h and 11.1±4.2L/h. For piperacillin, the PTA was ≥91% for doses ≥4.5g q8h at MICs≤16 μg/mL. For tazobactam, the PTA was 57%, 84% and 94% for doses of 4.5, 6.75 and 9.0g q8h, respectively. The pharmacokinetics of piperacillin and tazobactam are altered in obese patients. To ensure adequate tazobactam concentrations for β-lactamase inhibition, it may be prudent to employ larger initial doses for empirical therapy in obese patients.
authors.affiliation: St Francis Hospital, Department of Pharmacy, Indianapolis, IN, USA.
authors.forename: S Christian
authors.initials: SC
authors.lastname: Cheatham
authors.forename: Megan R
authors.initials: MR
authors.lastname: Fleming
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.forename: Christina E K
authors.initials: CE
authors.lastname: Chung
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Shea
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Humphrey
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009765:Obesity; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin