Investigation Monte Carlo Simulation for 3 Compartment Model as Biology System in Urinary

ABSTRACTAntibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia (VAP). Surprisingly few studies have quantified the penetration of β-lactam agents into the lung, as measured by the ratio of area under the concentration-time curve (AUC) in epithelial lining fluid (ELF) to AUC in plasma (AUCELF/AUCplasmaratio). These have typically involved noninfected patients. This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP. Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer (big nonparametric adaptive grid [BigNPAG]). A Monte Carlo simulation was performed to estimate the range of ELF/plasma penetration ratios one would expect to observe in patients with VAP, as measured by the AUCELF/AUCplasmaratio. The range of AUCELF/AUCplasmapenetration ratios predicted by the Monte Carlo simulation was large. The 10th percentile of lung penetration was 3.7%, while the 90th percentile of penetration was 178%. The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria likePseudomonas aeruginosa, then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population.

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Monte Carlo Simulation of a Compartment Model of Radionuclide Migration at a Radioactive Waste Repository

ASME 2009 12th International Conference on Environmental Remediation and Radioactive Waste Management, Volume 1 ◽

10.1115/icem2009-16168 ◽

2009 ◽

Author(s):

Francesco Cadini ◽

Jacopo De Sanctis ◽

Enrico Zio ◽

Diana Avram ◽

Tommaso Girotti ◽

...

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Value Added ◽

Compartment Model ◽

Simulation Approach ◽

Radionuclide Migration ◽

Modeling Framework ◽

Waste Repository ◽

Set Up ◽

Waste Repositories

Prediction of radionuclides release is a central issue in the performance assessment of nuclear waste repositories. To this aim a model of radionuclides migration through the repository barriers must be set up, accounting for the uncertainties affecting the process. In this context, the present paper presents the application of Monte Carlo simulation to a Markovian modeling framework proposed in the literature; two cases are presented to highlight the value added by the flexibility of the Monte Carlo simulation approach.

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Pharmacokinetics and Monte Carlo Simulation of Meropenem in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.768912 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jae Ha Lee ◽

Dong-Hwan Lee ◽

Jin Soo Kim ◽

Won-Beom Jung ◽

Woon Heo ◽

...

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Extracorporeal Membrane Oxygenation ◽

Creatinine Clearance ◽

Critically Ill ◽

Compartment Model ◽

Standard Regimen ◽

Dosage Regimens ◽

Two Compartment Model ◽

Population Pk

Objectives: There have been few clinical studies of ECMO-related alterations of the PK of meropenem and conflicting results were reported. This study investigated the pharmacokinetics (PK) of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation (ECMO) and used Monte Carlo simulations to determine appropriate dosage regimens.Methods: After a single 0.5 or 1 g dose of meropenem, 7 blood samples were drawn. A population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment was evaluated using Monte Carlo simulation. The following treatment targets were evaluated: the cumulative percentage of time during which the free drug concentration exceeds the minimum inhibitory concentration of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4xMIC.Results: Meropenem PK were adequately described by a two-compartment model, in which creatinine clearance and ECMO flow rate were significant covariates of total clearance and central volume of distribution, respectively. The Monte Carlo simulation predicted appropriate meropenem dosage regimens. For a patient with a creatinine clearance of 50–130 ml/min, standard regimen of 1 g q8h by i. v. infusion over 0.5 h was optimal when a MIC was 4 mg/L and a target was 40% fT>MIC. However, the standard regimen did not attain more aggressive target of 100% fT>MIC or 100% fT>4xMIC.Conclusion: The population PK model of meropenem for patients on ECMO was successfully developed with a two-compartment model. ECMO patients exhibit similar PK with patients without ECMO. If more aggressive targets than 40% fT>MIC are adopted, dose increase may be needed.

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Penetration of Vancomycin into Epithelial Lining Fluid in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00712-11 ◽

2011 ◽

Vol 55 (12) ◽

pp. 5507-5511 ◽

Cited By ~ 37

Author(s):

Thomas P. Lodise ◽

George L. Drusano ◽

Jill M. Butterfield ◽

Joshua Scoville ◽

Mark Gotfried ◽

...

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Healthy Volunteers ◽

Compartment Model ◽

Epithelial Lining ◽

Time Curve ◽

Epithelial Lining Fluid ◽

Content Type ◽

Concentration Time ◽

Few Data

ABSTRACTAlthough vancomycin is often regarded as an agent that concentrates poorly in the lower respiratory tract, as determined from concentrations in epithelial lining fluid (ELF), few data are available. This study sought to determine the profile of vancomycin exposure in the ELF relative to plasma. Population modeling and Monte Carlo simulation were employed to estimate the penetration of vancomycin into ELF. Plasma and ELF pharmacokinetic (PK) data were obtained from 10 healthy volunteers. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer using the big nonparametric adaptive grid (BigNPAG) program. Monte Carlo simulation with 9,999 subjects was performed to calculate the ELF/plasma penetration ratios by estimating the area under the concentration-time curve (AUC) in ELF (AUCELF) and plasma (AUCplasma) after a single simulated 1,000-mg dose. The mean (standard deviation) AUCELF/AUCplasmapenetration ratio was 0.675 (0.677), and the 25th, 50th, and 75th percentile penetration ratios were 0.265, 0.474, and 0.842, respectively. Our results indicate that vancomycin penetrates ELF at approximately 50% of plasma levels. To properly judge the adequacy of current doses and schedules employed in practice, future studies are needed to delineate the PK/PD (pharmacodynamics) target for vancomycin in ELF. If the PK/PD target in ELF is found to be consistent with the currently proposed target of an AUC/MIC of ≥400, suboptimal probability of target attainment would be expected when vancomycin is utilized for pneumonias due to MRSA (methicillin-resistantStaphylococcus aureus) with MICs in excess of 1 mg/liter.

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Electron Scattering in Solids

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100133618 ◽

1990 ◽

Vol 48 (2) ◽

pp. 4-5

Author(s):

Ryuichi Shimizu ◽

Ze-Jun Ding

Keyword(s):

Monte Carlo Simulation ◽

Monte Carlo ◽

Angular Distribution ◽

Elastic Scattering ◽

Electron Scattering ◽

Cross Sections ◽

Expansion Method ◽

Electron Excitation ◽

Partial Wave Expansion ◽

Backscattered Electrons

Monte Carlo simulation has been becoming most powerful tool to describe the electron scattering in solids, leading to more comprehensive understanding of the complicated mechanism of generation of various types of signals for microbeam analysis.The present paper proposes a practical model for the Monte Carlo simulation of scattering processes of a penetrating electron and the generation of the slow secondaries in solids. The model is based on the combined use of Gryzinski’s inner-shell electron excitation function and the dielectric function for taking into account the valence electron contribution in inelastic scattering processes, while the cross-sections derived by partial wave expansion method are used for describing elastic scattering processes. An improvement of the use of this elastic scattering cross-section can be seen in the success to describe the anisotropy of angular distribution of elastically backscattered electrons from Au in low energy region, shown in Fig.l. Fig.l(a) shows the elastic cross-sections of 600 eV electron for single Au-atom, clearly indicating that the angular distribution is no more smooth as expected from Rutherford scattering formula, but has the socalled lobes appearing at the large scattering angle.

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Determination of Stoichiometry of GaAs Component in (Gaas)Ge Epitaxially Grown Thin Films by Electron Microprobe X-Ray Analysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100134922 ◽

1990 ◽

Vol 48 (2) ◽

pp. 264-265

Author(s):

D. R. Liu ◽

S. S. Shinozaki ◽

R. J. Baird

Keyword(s):

Thin Film ◽

Thin Films ◽

Monte Carlo Simulation ◽

Monte Carlo ◽

Compound Semiconductors ◽

Energy Dispersive Analysis ◽

X Ray ◽

Metastable Alloys ◽

Lower Voltage

The epitaxially grown (GaAs)Ge thin film has been arousing much interest because it is one of metastable alloys of III-V compound semiconductors with germanium and a possible candidate in optoelectronic applications. It is important to be able to accurately determine the composition of the film, particularly whether or not the GaAs component is in stoichiometry, but x-ray energy dispersive analysis (EDS) cannot meet this need. The thickness of the film is usually about 0.5-1.5 μm. If Kα peaks are used for quantification, the accelerating voltage must be more than 10 kV in order for these peaks to be excited. Under this voltage, the generation depth of x-ray photons approaches 1 μm, as evidenced by a Monte Carlo simulation and actual x-ray intensity measurement as discussed below. If a lower voltage is used to reduce the generation depth, their L peaks have to be used. But these L peaks actually are merged as one big hump simply because the atomic numbers of these three elements are relatively small and close together, and the EDS energy resolution is limited.

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