Optimized chloroquine phosphate dosage regimens for early virological clearance of severe acute respiratory syndrome coronavirus 2 using Monte Carlo simulation

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.

Download Full-text

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

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz192 ◽

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.

Download Full-text

Evaluating amikacin dosage regimens in intensive care unit patients: A pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2013.04.021 ◽

2013 ◽

Vol 42 (2) ◽

pp. 155-160 ◽

Cited By ~ 10

Author(s):

Hinojal Zazo ◽

Ana Martín-Suárez ◽

José M. Lanao

Keyword(s):

Intensive Care Unit ◽

Monte Carlo Simulation ◽

Monte Carlo ◽

Intensive Care ◽

Dosage Regimens ◽

Pharmacodynamic Analysis

Download Full-text

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.

Download Full-text

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.

Download Full-text