Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections 

Abstract

BackgroundFor more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients’ characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections.Materials and MethodsAt least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CLcr) ≤50 ml/min or CLcr >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P <0.05 for selection and P <0.01 for elimination.ResultsBoth piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CLcr /47 for piperacillin and CL = 1.76 + 4.81 × CLcr /47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam.ConclusionThe PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.

Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Simulation of Piperacillin/Tazobactam for Dosing Optimization in Late Elderly Patients with Pneumonia

“…In this study, the CL values for late elderly patients estimated from the population parameters and mean CL cr values were 4.62 and 5.04 L/h for PIPC and TAZ, respectively. These are lower than the values of PIPC (5.36 to 18.02 L/h) and TAZ (6.95 to 8.03 L/h) in adults including young and elderly patients, which was reported in previous papers [10,[12][13][14][15]17]. This may be due to age-related changes in the elimination process, namely decreased renal function.…”

“…The PK models of PIPC and TAZ have been previously described by both one- [16,18,19] and two-compartment models [10,[12][13][14][15]17]. In our study, plasma-concentration-time data were analyzed by a two-compartment model because the AIC values of the two-compartment model (1040.069, PIPC and 596.955, TAZ) were lower than those of the one-compartment model (1063.038, PIPC and 615.059, TAZ).…”

“…Some population PK studies concerning PIPC/TAZ in adult subjects have been reported [10][11][12][13][14][15][16][17][18][19]. In many antibiotics, including carbapenems and cephems, elderly patients have been reported to have different PK parameters than younger patients [21][22][23].…”

“…Establishing a population PK model is necessary in planning an optimized therapeutic regimen. Population PK models on PIPC/TAZ have been reported in young adult patients with nosocomial infections [10,11], sepsis [12,13], febrile neutropenia [14], acute infections [15], and obesity [16], and those undergoing continuous renal replacement therapy [17]. Additionally, antimicrobial chemotherapy with a combination of a β-lactam/β-lactamase inhibitor requires that there is a sufficient amount of the inhibitor to inactivate β-lactamases, which allows the β-lactam to exhibit its antibacterial activity [18].…”

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

“…A flowchart of study selection for each drug is provided in Figure . A total of 2082 articles were identified and screened, with 130 studies included in the final analysis . Some studies provided PK parameters for two drugs (e.g.…”