scholarly journals Dosing regimens of oral ciprofloxacin for children with severe malnutrition: a population pharmacokinetic study with Monte Carlo simulation

2011 ◽  
Vol 66 (10) ◽  
pp. 2336-2345 ◽  
Author(s):  
N. Thuo ◽  
W. Ungphakorn ◽  
J. Karisa ◽  
S. Muchohi ◽  
A. Muturi ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Pharmacokinetic Study ◽  
Severe Malnutrition ◽  
Population Pharmacokinetic ◽  
Population Pharmacokinetic Study ◽  
Dosing Regimens ◽  
Oral Ciprofloxacin

scholarly journals Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Du ◽  
Yue Zhou ◽  
Bo-Hao Tang ◽  
Yue-E Wu ◽  
Xin-Mei Yang ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Pharmacokinetic Study ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Augmented Renal Clearance ◽  
Population Pharmacokinetic Study ◽  
Dosing Regimens

Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine.Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program.Results: The data (n = 36) from 20 infants (age range, 0.35–1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09–0.29) L/h/kg and 0.34 (0.24–0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively.Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.

scholarly journals Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1559
Author(s):  
Francisco Beraldi-Magalhaes ◽  
Suzanne L. Parker ◽  
Cristina Sanches ◽  
Leandro Sousa Garcia ◽  
Brenda Karoline Souza Carvalho ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Oral Absorption ◽  
Compartment Model ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Population Pharmacokinetic ◽  
Icu Patients ◽  
Population Pharmacokinetic Study ◽  
Dosing Regimens ◽  
Dose Combination

Background: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. Methods: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC/MIC > 11.9 and Cmax/MIC > 0.48 values. Optimized dosing regimens were simulated at steady state. Results: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p < 0.05). Mean bioavailability for ICU patients was >5-times higher than outpatients (p < 0.0001). Clearance and volume of distribution were 93% (p < 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. Conclusions: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.

scholarly journals Remedial dosing recommendation for delayed or missed rivaroxaban doses for patients with non-valvular atrial fibrillation based on Monte Carlo simulation

2020 ◽  
Author(s):  
Xiao-qin Liu ◽  
Yin-wei Yin ◽  
Chen-yu Wang ◽  
Zi-ran Li ◽  
Xiao Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Factor Xa ◽  
Heart Rhythm ◽  
Population Pharmacokinetic ◽  
Dosing Regimen ◽  
Drug Concentrations ◽  
Simulation Based ◽  
Dosing Regimens

Background Rivaroxaban is a non-vitamin K oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier for patients to maximise the benefit of their medications. This study aimed to explore appropriate remedial dosing regimens for rivaroxaban-treated patients with NVAF. Methods Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic model for patients with NVAF was employed to design remedial dosing regimens. Both the European Heart Rhythm Association (EHRA) recommendations and the model were used to establish remedial dosing regimens, which were assessed considering the on-therapy range of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results Recommendations of EHRA guide may not be optimal. Our findings suggested that a missed dose is taken immediately when the delay is less than or equal to 6 h; a half dose is advisable when the delay exceeds 6 h but is less than 4 h before the next dose. It is recommended to skip a dose when there are less than 4 h before the next dose. Age or renal function do not significantly influence the remedial dosing regimen. Conclusion A remedial dosing regimen based on model-based Monte Carlo simulation was systematically developed for rivaroxaban-treated patients with NVAF with poor adherence to quickly restore drug concentrations to the on-therapy range and to reduce the risk of bleeding and thromboembolism.

scholarly journals Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study

Critical Care ◽  
2018 ◽  
Vol 22 (1) ◽  
Author(s):  
Stephan Braune ◽  
Christina König ◽  
Jason A. Roberts ◽  
Axel Nierhaus ◽  
Oliver Steinmetz ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Population Pharmacokinetic ◽  
Population Pharmacokinetic Study ◽  
Low Efficiency
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