Evaluating posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation

2020 ◽  
Vol 56 (4) ◽  
pp. 106112
Author(s):  
Xiao-Chen Wei ◽  
Ming-Feng Zhao ◽  
Xin Li ◽  
Xia Xiao
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Pharmacodynamic Analysis ◽  
Dosing Regimens

scholarly journals Pharmacokinetic/pharmacodynamic analysis of weight- and height-scaled tobramycin dosage regimens for patients with cystic fibrosis

2019 ◽  
Vol 74 (8) ◽  
pp. 2311-2317
Author(s):  
S S Alghanem ◽  
D J Touw ◽  
A H Thomson
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Simulated Dataset ◽  
Dosage Regimens ◽  
Pharmacodynamic Analysis ◽  
Dosing Regimens ◽  
Lower Height ◽  
Higher Doses

Abstract Objectives To determine the outcomes of weight- and height-based tobramycin dosing regimens for patients with cystic fibrosis (CF). Methods A simulated dataset of 5000 patients based on 331 patients with CF was created using NONMEM. Pharmacokinetic (PK) parameters were derived for each patient from a published model using Monte Carlo simulation. The abilities of 10 and 12 mg/kg/day and 3 and 4 mg/cm/day to achieve standard and extended Cmax (20–30 and 20–40 mg/L) and AUC0–24 (80–120 and 80–150 mg·h/L) targets were evaluated. PK/pharmacodynamic (PK/PD) indices were a Cmax/MIC ratio ≥10 and an AUC0–24/MIC ratio ≥110. For these indices and a range of MICs, cumulative fractions of response (CFRs) for Pseudomonas aeruginosa were also determined. Results More patients achieved standard Cmax and AUC0–24 targets with 3 mg/cm/day (64% and 62%, respectively) than with 10 mg/kg/day (43% and 48%, respectively). AUC0–24 estimates >120 mg·h/L were more common with weight-based dosing. With higher doses, 72% achieved high target peaks with 4 mg/cm/day and 65% with 12 mg/kg/day. For the Cmax/MIC index, the maximal MIC for the target microorganism was 2 mg/L with lower doses, 2.5 mg/L with higher doses and 0.5 mg/L for AUC0–24/MIC-based regimens. The CFR for all regimens was >90% for Cmax targets and 66% to 79% for AUC0–24 targets. Conclusions A tobramycin dose of 3 mg/cm/day rather than 10 mg/kg/day achieved similar PK/PD outcomes but dose and AUC0–24 ranges were narrower and the incidence of high AUC0–24 values was lower. Height-based doses should therefore be considered for patients with CF.

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
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