Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation

2012 ◽  
Vol 40 (4) ◽  
pp. 344-348 ◽  
Author(s):  
Takaaki Yamada ◽  
Toshiharu Nonaka ◽  
Takahisa Yano ◽  
Toshio Kubota ◽  
Nobuaki Egashira ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Dosing Regimens ◽  
Patient Groups

Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function

2016 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Abrar K. Thabit ◽  
Mordechai Grupper ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Inhibitory Concentration ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Function Range ◽  
Prescribing Information

Objectives: To evaluate the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens. Methods: A 5000-patient Monte Carlo simulation was conducted to determine the probability of achieving 50% free time above the minimum inhibitory concentration ( fT > MIC) for piperacillin. Proposed regimens, using solely 4.5 or 3.375 g strengths, were compared with regimens listed in piperacillin/tazobactam prescribing information over creatinine clearance (CrCl) ranges of 120 mL/min to hemodialysis. The probability of target attainment (PTA) at MICs ≤ 16 μg/mL was compared between proposed and standard regimens. Results: At CrCl 41 to 120 mL/min, prolonged infusions of 4.5 g (3 hours) and 3.375 g (4 hours) every 6 hours resulted in ≥95% PTA versus ≥76% for standard regimens (0.5 hour). At CrCl 20 to 40 mL/min, 4.5 and 3.375 g every 8 hours as prolonged infusions achieved slightly higher PTA (≥98%) versus standard regimens (≥93%). Similarly, PTA achieved with prolonged infusions of 4.5 and 3.375 g every 12 hours (≥93%) was comparable with those of standard regimens (≥91%) at CrCl 1 to 19 mL/min. In hemodialysis, 100% PTA was achieved with prolonged infusion regimens. Conclusion: Piperacillin/tazobactam regimens designed around the 4.5 or 3.375 g dose and prolonged infusions provided similar or better PTA at MICs ≤ 16 μg/mL compared with standard regimens. These observations may support the stocking and use of a single piperacillin/tazobactam strength to simplify dosing.

scholarly journals Fosfomycin Dosing Regimens based on Monte Carlo Simulation for Treated Carbapenem-Resistant Enterobacteriaceae Infection

2020 ◽  
Vol 52 (4) ◽  
pp. 516
Author(s):  
Sukrit Kanchanasurakit ◽  
Wichai Santimaleeworagun ◽  
Charles E. McPherson ◽  
Napacha Piriyachananusorn ◽  
Benjawan Boonsong ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Carbapenem Resistant ◽  
Dosing Regimens ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Dong-Hwan Lee ◽  
Yong Kyun Kim ◽  
Kyubok Jin ◽  
Myoung Joo Kang ◽  
Young-Don Joo ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Body Weight ◽  
The Body ◽  
Relative Standard Error ◽  
Dosing Regimen ◽  
Korean Patients ◽  
Acute Infections ◽  
Relative Standard

ABSTRACT We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CLCR. The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CLCR/57)0.688, where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.

Pharmacokinetic/Pharmacodynamic Analysis of Meropenem for the Treatment of Nosocomial Pneumonia in Intracerebral Hemorrhage Patients by Monte Carlo Simulation

2017 ◽  
Vol 51 (11) ◽  
pp. 970-975 ◽  
Author(s):  
Lingti Kong ◽  
Yan Tang ◽  
Xiaohua Zhang ◽  
Guoyu Lu ◽  
Meiling Yu ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Intracerebral Hemorrhage ◽  
Nosocomial Pneumonia ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Dosing Regimens ◽  
Total Body

Background: Nosocomial pneumonia (NP) is a frequent complication among patients with intracerebral hemorrhage (ICH). However, there are currently no pharmacokinetic (PK) and pharmacodynamic (PD) data to guide meropenem dosing in these patients. Objective: To investigate the PK/PD properties of meropenem in these patients and whether the usual dosing regimens of meropenem (2-hour infusion, 1 g, every 8 hours) was suitable. Methods: A total of 11 patients with a diagnosis of ICH complicated with NP were selected in the emergency internal medicine and treated with a 1-g/2-hours extended infusion model. The plasma concentrations of meropenem were determined by high-performance liquid chromatography. PK parameters were estimated by plasma concentration versus time profile using WinNonlin software. The probability of target attainments (PTAs) of meropenem at different minimum inhibitory concentrations (MICs) based on percentage time that concentrations were above the minimum inhibitory concentration (%T>MIC) value were performed by Monte Carlo simulation. Results: The volume of distribution and total body clearance of meropenem were 55.55 L/kg and 22.89 L/h, respectively. Using 40%T>MIC, PTA was >90% at MICs ≤4 µg/mL. Using 80% or 100%T>MIC, PTA was >90% only at MICs ≤1 µg/mL. Conclusions: The PK/PD profile of dosing regimens tested will assist in selecting the appropriate meropenem regimens for these patients. At a target of 40%T>MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤4 µg/mL. However, when a higher target (80% or 100%) is desired for difficult-to-treat infections, larger doses, prolonged infusions, shorter intervals, and/or combination therapy may be required.

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