population pharmacokinetic study
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Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1559
Author(s):  
Francisco Beraldi-Magalhaes ◽  
Suzanne L. Parker ◽  
Cristina Sanches ◽  
Leandro Sousa Garcia ◽  
Brenda Karoline Souza Carvalho ◽  
...  

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.


Author(s):  
Pier Giorgio Cojutti ◽  
Matteo Rinaldi ◽  
Eleonora Zamparini ◽  
Nicolò Rossi ◽  
Sara Tedeschi ◽  
...  

We thank Baklouti et al. (1) for commenting on our population pharmacokinetic study of dalbavancin for optimal treatment of adult patients with staphylococcal osteoarticular infections (2) and for suggesting that our model tends to underestimate the concentrations observed in a group of French patients (French group).…


2021 ◽  
Vol 08 ◽  
Author(s):  
Miriam Nayeli Morales-Barragán ◽  
María del Carmen Romero-Méndez ◽  
Rosa del Carmen Milán-Segovia ◽  
Jaime Guillermo Rodríguez-Rivera ◽  
María Angélica Aguilar-Torres ◽  
...  

Background: Metformin is the first-line drug to enhance glycemic control of type 2 diabetes mellitus (DM2) patients. Some reported methods to determine plasma metformin by HPLC-UV are not sensitive enough. Other methods require long extraction processes. Objective: The objective of this study was to develop and validate a simple and rapid analytical method to determine plasma metformin by HPLC-UV for application in a population pharmacokinetic study. Methods: Analyte was extracted from plasma by a simple protein precipitation technique using trichloroacetic acid (15%, w/v) as the precipitating agent. Plasma samples were analyzed using a C18 column (3.0 x 150 mm, 3.5 µm) under isocratic elution with 30 mM sodium hexansulfonate (pH 5) and acetonitrile (97: 3, v/v). Results: The limit of quantification (LOQ) was 0.1 µg mL-1 and the calibration curve was linear up to 4 µg mL-1 with a correlation coefficient >0.99. The mean recovery for metformin using this extraction procedure was 84.4 - 86.6%. The intra- and inter-day coefficients of variation and percent error values of the assayed method were <0% and <15% for LOQ and QCs, respectively. Metformin was stable in plasma samples by subjecting it to three freeze-thaw cycles and storing it up to 60 days at -80°C. This method was applied to determine plasma metformin concentrations in patients with type 2 diabetes mellitus treated with this drug. Conclusion: The HPLC-UV method developed is selective, accurate and precise for the quantification of metformin in plasma samples. Since sample, processing is fast and simple, in addition to being applicable in pharmacokinetic studies.


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