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.

Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function

2007 ◽  
Vol 97 (04) ◽  
pp. 581-586 ◽  
Author(s):  
Manvel Aghassarian ◽  
Ludovic Drouet ◽  
Claire dit-Sollier ◽  
Karine Lacut ◽  
Jean-Jacques Heilmann ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Elderly Patients ◽  
Creatinine Clearance ◽  
Impaired Renal Function ◽  
The Body ◽  
Accumulation Factor ◽  
Renal Elimination ◽  
Prophylactic Dose ◽  
Accumulation Effect

SummaryLow-molecular-weight heparins (LMWHs) accumulate in patients with impaired renal function. As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination, LMWHs might have different pharmacodynamic profiles. The primary objective was to examine if any accumulation effect of two LMWHs, enoxaparin and tinzaparin, occurred after repeated administration of a prophylactic dose over eight days in elderly patients (age >75 years) with creatinine clearance between 20 and 50 ml/min and body weight <65Kg. Patients were openly randomized to two groups (enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily). Anti-Xa was measured on day 1 and day 8. Blood samples were taken at 0, 2, 4, 5, 6, 9, 12, 16 and 24 hours. The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day 1and day 8. Fifty-five patients were included (mean age 87.9 ± 5.5 ).The creatinine clearance was 34.7 ± 11.4 ml/min; the body weight was 52.3 ± 8.6 kg. The accumulation factor defined was not significant for tinzaparin (1.05, p=0.29) while it was significantly enhanced for enoxaparin (1.22, p <0.0001). In this pharmacodynamic study performed in elderly patients with impaired renal function, a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin, which are two LMWHs with different chain lengths. Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations.

scholarly journals Establishing Standards for Studying Renal Function in Mice through Measurements of Body Size-Adjusted Creatinine and Urea Levels

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Wellington Francisco Rodrigues ◽  
Camila Botelho Miguel ◽  
Marcelo Henrique Napimoga ◽  
Carlo Jose Freire Oliveira ◽  
Javier Emilio Lazo-Chica
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Measurement Techniques ◽  
The Body ◽  
Urea Concentration ◽  
Time Points ◽  
Average Factor

Strategies for obtaining reliable results are increasingly implemented in order to reduce errors in the analysis of human and veterinary samples; however, further data are required for murine samples. Here, we determined an average factor from the murine body surface area for the calculation of biochemical renal parameters, assessed the effects of storage and freeze-thawing of C57BL/6 mouse samples on plasmatic and urinary urea, and evaluated the effects of using two different urea-measurement techniques. After obtaining 24 h urine samples, blood was collected, and body weight and length were established. The samples were evaluated after collection or stored at −20°C and −70°C. At different time points (0, 4, and 90 days), these samples were thawed, the creatinine and/or urea concentrations were analyzed, and samples were restored at these temperatures for further measurements. We show that creatinine clearance measurements should be adjusted according to the body surface area, which was calculated based on the weight and length of the animal. Repeated freeze-thawing cycles negatively affected the urea concentration; the urea concentration was more reproducible when using the modified Berthelot reaction rather than the ultraviolet method. Our findings will facilitate standardization and optimization of methodology as well as understanding of renal and other biochemical data obtained from mice.

scholarly journals An Investigation to Determine an Optimum Protective Garment Material in Nuclear Medicine

2018 ◽  
Vol 8 (4Dec) ◽  
Author(s):  
R Parvaresh ◽  
A Haghparast ◽  
K Khoshgard ◽  
M Jalili ◽  
M T Eivazi ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Nuclear Medicine ◽  
The Body ◽  
Dose Enhancement ◽  
Simulation Code ◽  
Radiation Attenuation ◽  
Optimum Material ◽  
Protective Garment

Aim: The aim of this study is to find an optimum material to protect garment for protection against 99Tcm radionuclide.Materials and Methods: Monte Carlo simulation code was applied to investigate radiation attenuation of 13 shielding materials including: Ba, gray Sn, white Sn, Sb, Bi, Bi2O3, BaSO4, Sn/W, Sb/W, Pb and W with thicknesses of 0.5 and 1 mm to determine an optimum protective garment material in nuclear medicine against 99Tcm. Furthermore, the dose enhancement on the staff body was investigated for shielding materials such as tungsten and lead.Results: The findings of the simulations show that the maximum and minimum attenuation obtained with thicknesses of 1 mm W and 1 mm BaSO4 were 96.46% and 14.2%, respectively. The results also demonstrate that tungsten does not cause any dose enhancement on staff body but this is not true for lead. Tungsten provides the highest radiation attenuation without dose enhancement on the body of staff.Conclusion: Among materials evaluated, tungsten is the optimum material and it can be applied for the design of protective garment for nuclear medicine staff against 99Tcm.

scholarly journals Population Pharmacokinetics of Piperacillin in the Early Phase of Septic Shock: Does Standard Dosing Result in Therapeutic Plasma Concentrations?

2015 ◽  
Vol 59 (11) ◽  
pp. 7018-7026 ◽  
Author(s):  
Kristina Öbrink-Hansen ◽  
Rasmus Vestergaard Juul ◽  
Merete Storgaard ◽  
Marianne Kragh Thomsen ◽  
Tore Forsingdal Hardlei ◽  
...  
Keyword(s):  
Septic Shock ◽  
Renal Function ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
Pharmacokinetic Profile ◽  
Population Pharmacokinetic ◽  
Relative Standard Error ◽  
Content Type ◽  
Relative Standard ◽  
Dosing Regimens

ABSTRACTAntibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC forPseudomonas aeruginosa(16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50%fT>4×MIC and 100%fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.)

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 Optimized dosing regimen of hydroxychloroquine for treatment of coronavirus disease 2019 using Monte Carlo simulation

2021 ◽  
Vol 48 (5) ◽  
pp. 425-431
Author(s):  
Sumit Leevanichchakhul ◽  
Pitchaya Dilokpattanamongko ◽  
Taniya Paiboonvong ◽  
Suwida Tangtrakultham ◽  
Supatat Chumnumwat ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Dosing Regimen

Chemometrics and Monte-Carlo Simulation Assisted RP-LC Method for Estimation of Cinacalcet Hydro- chloride in Pharmaceutical Products

2021 ◽  
Vol 14 (2) ◽  
pp. 5436-5447
Author(s):  
Ravi Kumar Venkata Varaha Bera ◽  
Sagar Suman Panda
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Drug Product ◽  
Control Strategies ◽  
Scientific Information ◽  
Pharmaceutical Products ◽  
Method Performance ◽  
Pharmaceutical Dosage Form ◽  
Relative Standard ◽  
Cinacalcet Hydrochloride

Cinacalcet hydrochloride (CNT) is a novel calcimimetic agent widely used in the treatment of hyperparathy- roidism. For the first time, the authors utilized the novel concept of analytical procedure development employing several unique scientific tools for quantification CNT from its pharmaceutical dosage form. The objective behind the present work was to establish a scientifically sound and systematic work frame that overcomes the drawbacks of the earlier reported method for estimating CNT level in samples and ensuring superior method performance throughout the analytical life-cycle. In this  process, at first, the risky method variables were earmarked and were subjected to a response surface methodology, followed by Monte-Carlo simulation (MCS) based robust- ness-cum-optimization studies. The inclusion of the MCS approach assessed the method performance with no additional laboratory experimentation  and  established the innovative hyphenation's aptness with chemometrics tools. The control strategies were established based on analytical design space and method performance evaluation results by a simulative approach. The study revealed that methanol %, flow rate, and pH are the three critical method variables influencing analytical attributes: retention time, the number of plates, and tailing. The analytical conditions include a C18 column (150mm × 4.6mm, 5μm) with an isocratic mobile phase (80:20, % v/v) of methanol and 0.01M KH2PO4 buffer (pH maintained at 3.5 using orthophosphoric acid) flowing at 1.1ml/min. Diode array detection was performed at 282 nm. Method validation was befitting to federal needs as linearity (0.5-160 μg/ml), accuracy (>99%), and precision below 1% of relative standard deviation are indicative of method suitability for the purpose. In a nutshell, the present method describes a typical analytical workflow with the significant advantage of  obtaining  more excellent scientific information with less systematized experimentation. It was found suitable for routine quality control of CNT in drug substance and drug product.

scholarly journals Determining optimal dosing regimen of oral administration of dicloxacillin using Monte Carlo simulation

2017 ◽  
Vol Volume 11 ◽  
pp. 1951-1956 ◽  
Author(s):  
Wei Yu ◽  
Jinru Ji ◽  
Tingting Xiao ◽  
Chaoqun Ying ◽  
Jiaheng Fang ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Oral Administration ◽  
Dosing Regimen ◽  
Optimal Dosing
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