Pharmacokinetic Parameter Original Result

Background. Meropenem, a broad spectrum carbapenem antibiotic, is often used for newborns despite of limited data available on neonatal pharmacokinetics. Due to pharmacokinetic and pharmacodynamic differences as well as to significant changes in the human body related to growth and maturation of organs and systems, direct scaling and dosing extrapolation from adults or older children with adjustment on patients weight can result in increased risk of toxicity or treatment failures. Aims to evaluate the pharmacokinetics of meropenem in premature neonates based on therapeutic drug monitoring data in real clinical settings. Materials. Of 53 pre-term neonates included in the pharmacokinetic/pharmacodynamic analysis, in 39 (73.6%) patients, gestational age ranged from 23 to 30 weeks. Population and individual pharmacokinetic parameter values were estimated by the NPAG program from the Pmetrics package based on peak-trough therapeutic drug monitoring. Samples were assayed by high-performance liquid chromatography. One-compartment pharmacokinetic model with zero-order input and first-order elimination was used to fit concentration data and to predict pharmacokinetic parameter (%T MIC of free drug) for virtual patients with simulated fast, moderate and slow meropenem elimination received different dosage by minimum inhibitory concentration (MIC) level. Univariate and multivariate regression analysis was used to evaluate the influence of patients covariates (gestational age, postnatal age, postconceptual age, body weight, creatinine clearance calculated by Schwartz formula, etc) on estimated meropenem pharmacokinetic parameters. Results. The identified population pharmacokinetic parameters of meropenem in pre-term newborns (elimination half-lives T1/2 = 1.93 0.341 h; clearance CL = 0.26 0.085 L/h/ kg; volume of distribution V = 0.71 0.22 L/h) were in good agreement with those published in the literature for adults, neonates and older children. Pharmacokinetic/pharmacodynamic modeling demonstrated that a meropenem dosage regimen of 90 mg/kg/day administered using prolonged 3-hour infusion every 8 hours should be considered as potentially effective therapy if nosocomial infections with resistant organisms (MIC 8 mg/L) are treated. Conclusions. Neonates and especially pre-term neonates have a great pharmacokinetic variability. Meropenem dosing in premature newborns derived from population pharmacokinetic/pharmacodynamic model can partly overcome the variability, but not all pharmacokinetic variability can be explained by covariates in a model. Further personalizing based on Bayesian forecasting approach and a patients therapeutic drug monitoring data can help to achieve desired pharmacodynamic target.

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Concept of education of a creative personality

All Ukrainian scientific-practical magazine Principal of School Liceum Gymnasium ◽

10.37836/2309-7744-2020-1-5 ◽

2020 ◽

pp. 50-55

Author(s):

V.О. Moliako

Keyword(s):

Enriched Environment ◽

Reference Points ◽

Creative Activity ◽

Environmental Friendliness ◽

Original Result ◽

Creative Education ◽

Creative Personality ◽

Specific Stage ◽

Systematic Solution ◽

Human Spirituality

At each specific stage of society development, certain guidelines dominate, which set the direction in solving the problems of educating the younger generation. We are deeply convinced that today such reference points are the creative and aesthetic factors that determine the basis of human spirituality. The essence of the proposed conception is education, an integral component of which is the systematic solution of various creative tasks in an aesthetically enriched environment. The pupils’ coordinated with age creative activity will contribute to increasing the motivation to work, developing the intellect, maximizing the abilities of each of them. Creative education, as it is understood here, involves the use of different methods, approaches to the child and its orientation towards achieving the most original result during the performance of any work, finding as many possible solutions for each new task as possible, comparing them to each other, choosing the best by the sum of specific indicators (profitability, environmental friendliness, aesthetics, etc.). In this context, creativity is also understood as ordinary work, the consequences of which are necessary for both the performer himself and other people. In some cases it is necessary to use special techniques of creative training KARUS.

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