A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid. The method was validated for parameters including linearity, accuracy, precision, limit of quantitation and limit of detection, as well as robustness. The response was found linear over the range of 3-100 μg/mL as demonstrated by the acquired value of correlation coefficient R2=0.9997. The described method is applicable for determination of various pharmacokinetic aspects of ketoprofen in vitro.
The performance of a pharmaceutical formulation, such as the drug (API) release rate, is significantly influenced by the properties of the materials used, the composition of the final product and the tablet compression process parameters. However, in some cases, the knowledge of these input parameters does not necessarily provide a reliable description or prediction of tablet performance. Therefore, the knowledge of tablet microstructure is desirable to understand such formulations. Commonly used analytical techniques, such as X-ray tomography and intrusion mercury porosimetry, are not widely used in pharmaceutical companies due to their price and/or toxicity, and therefore, efforts are made to develop a tool for fast and easy microstructure description. In this work, we have developed an image-based method for microstructure description and applied it to a model system consisting of ibuprofen and CaHPO4∙2H2O (API and excipient with different deformability). The obtained parameter, the quadratic mean of the equivalent diameter of the non-deformable, brittle excipient CaHPO4∙2H2O, was correlated with tablet composition, compression pressure and API release rate. The obtained results demonstrate the possibility of describing the tablet dissolution performance in the presented model system based on the microstructural parameter, providing a possible model system for compressed solid dosage forms in which a plastic component is present and specific API release is required.
- MeSH
- biologické modely * MeSH
- ibuprofen chemie MeSH
- pomocné látky * chemie MeSH
- příprava léků MeSH
- tablety chemie MeSH
- Publikační typ
- časopisecké články MeSH
Bolest je nepříjemný senzorický, emoční a mentální prožitek doprovázený psychickými či vegetativními reakcemi a změnou chování. Proto je nutné bolest efektivně léčit nefarmakologickými i farmakologickými postupy. Farmakoterapie v dětském věku má řadu zvláštností, v následujícím článku stručně shrneme možnosti farmakologické léčby u dětí, používaná neopioidní a opioidní analgetika, jejich vlastnosti a dávkování vybraných perorálních analgetik.
Pain is distressing sensory, emotional and mental experience accompanied by psychological or autonomic symptoms and change of behavior. It is therefore necessary to effectively treat pain using nonpharmacological and pharmacological methods. Pediatric pharmacotherapy has many peculiarities, in the following article we summarize pharmacological treatment options in children, currently used nonopioid and opioid analgesics, their characteristics and the dosage of selected orally used analgesics.
- MeSH
- antiflogistika nesteroidní aplikace a dávkování terapeutické užití MeSH
- bolest * farmakoterapie MeSH
- dítě * MeSH
- ibuprofen aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- management bolesti MeSH
- nežádoucí účinky léčiv MeSH
- opioidní analgetika aplikace a dávkování terapeutické užití MeSH
- paracetamol aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě * MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Stem cells represent promising candidates for regenerative therapy of craniomaxillofacial bone defects, where common techniques, such as autogenous bone graft, allografts or others possess shortcomings and limitations in restoring the morphology and function in bone loss. The efficacy of regenerative therapy with mesenchymal stromal cells (MSC) depends on a combination of the interactions between transplanted MSCs and cellular and molecular components of the recipient, and any current pharmacotherapy in the recipient with effects on transplanted MSC and the bone microenvironment. In the present investigation, dental pulp stem cells (DPSC) were isolated from human impacted third molar teeth. DPSC were treated with ibuprofen in vitro at clinically relevant concentration and relative expression of selected genes were assessed. Our preliminary data suggest a significant effect of ibuprofen as indicated by upregulation of the relative expression levels of growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). While the effects of stem cell therapy in bone regeneration are being investigated in ongoing clinical trials, the effects of commonly used pharmacotherapy should be studied for its potential impact on the paracrine effects of stem cells and consequently bone regenerative processes.
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- exprese genu MeSH
- hepatocytární růstový faktor MeSH
- ibuprofen * terapeutické užití MeSH
- kmenové buňky MeSH
- lebka patologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- nemoci kostí farmakoterapie terapie MeSH
- parakrinní signalizace MeSH
- polymerázová řetězová reakce MeSH
- regenerativní lékařství metody MeSH
- techniky in vitro metody MeSH
- vaskulární endoteliální růstový faktor A MeSH
- Check Tag
- lidé MeSH
One of the main contributors to pharmaceutical pollution of surface waters are non-steroidal anti-inflammatory drugs (NSAIDs) that contaminate the food chain and affect non-target water species. As there are not many studies focusing on toxic effects of NSAIDs on freshwater fish species and specially effects after dietary exposure, we selected rainbow trout (Oncorhynchus mykiss) as the ideal model to examine the impact of two NSAIDs - diclofenac (DCF) and ibuprofen (IBP). The aim of our study was to test toxicity of environmentally relevant concentrations of these drugs together with exposure doses of 100× higher, including their mixture; and to deepen knowledge about the mechanism of toxicity of these drugs. This study revealed kidneys as the most affected organ with hyalinosis, an increase in oxidative stress markers, and changes in gene expression of heat shock protein 70 to be signs of renal toxicity. Furthermore, hepatotoxicity was confirmed by histopathological analysis (i.e. dystrophy, congestion, and inflammatory cell increase), change in biochemical markers, increase in heat shock protein 70 mRNA, and by oxidative stress analysis. The gills were locally deformed and showed signs of inflammatory processes and necrotic areas. Given the increase in oxidative stress markers and heat shock protein 70 mRNA, severe impairment of oxygen transport may be one of the toxic pathways of NSAIDs. Regarding the microbiota, an overgrowth of Gram-positive species was detected; in particular, significant dysbiosis in the Fusobacteria/Firmicutes ratio was observed. In conclusion, the changes observed after dietary exposure to NSAIDs can influence the organism homeostasis, induce ROS production, potentiate inflammations, and cause gut dysbiosis. Even the environmentally relevant concentration of NSAIDs pose a risk to the aquatic ecosystem as it changed O. mykiss health parameters and we assume that the toxicity of NSAIDs manifests itself at the level of mitochondria and proteins.
- MeSH
- antiflogistika nesteroidní metabolismus MeSH
- biologické markery metabolismus MeSH
- chemické látky znečišťující vodu * metabolismus MeSH
- diklofenak metabolismus MeSH
- dysbióza MeSH
- ekosystém MeSH
- epidemický výskyt choroby MeSH
- ibuprofen metabolismus toxicita MeSH
- kyslík metabolismus MeSH
- léčivé přípravky metabolismus MeSH
- messenger RNA metabolismus MeSH
- Oncorhynchus mykiss * metabolismus MeSH
- oxidační stres MeSH
- proteiny tepelného šoku HSP70 metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- střevní mikroflóra * MeSH
- voda metabolismus MeSH
- zánět chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this study, two capillary electrophoresis-based ligand binding assays, namely, mobility shift affinity capillary electrophoresis (ms-ACE) and capillary electrophoresis-frontal analysis (CE-FA), were applied to determine binding parameters of human serum albumin toward small drugs under similar experimental conditions. The substances S-amlodipine (S-AML), lidocaine (LDC), l-tryptophan (l-TRP), carbamazepine (CBZ), ibuprofen (IBU), and R-verapamil (R-VPM) were used as the main binding partners. The scope of this comparative study was to estimate and compare both the assays in terms of their primary measure's precision and the reproducibility of the derived binding parameters. The effective mobility could be measured with pooled CV values between 0.55% and 7.6%. The precision of the r values was found in the range between 1.5% and 10%. Both assays were not universally applicable. The CE-FA assay could successfully be applied to measure the drugs IBU, CBZ, and LDC, and the interaction toward CBZ, S-AML, l-TRP, and R-VPM could be determined using ms-ACE. The average variabilities of the estimated binding constants were 64% and 67% for CE-FA and ms-ACE, respectively.
- MeSH
- akutní myeloidní leukemie * MeSH
- elektroforéza kapilární metody MeSH
- ibuprofen MeSH
- izotachoforéza * MeSH
- lidé MeSH
- lidský sérový albumin metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- tryptofan MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- bolest * diagnóza farmakoterapie patologie MeSH
- dítě MeSH
- ibuprofen farmakokinetika farmakologie terapeutické užití MeSH
- lidé MeSH
- měření bolesti klasifikace MeSH
- neopioidní analgetika * aplikace a dávkování dějiny farmakologie klasifikace MeSH
- paracetamol aplikace a dávkování dějiny farmakologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
Conversion to mucoid form is a crucial step in the pathogenesis of P. aeruginosa in burns and cystic fibrosis (CF) patients. Alginate is considered the major component of biofilm and is highly associated with the formation of mucoid biofilm in this species. Nonsteroid anti-inflammatory drugs (NSAIDs), including ibuprofen, have shown promising antibacterial and antibiofilm potential for bacterial pathogens. In this study, we aimed to evaluate the effect of ibuprofen on the expression of alginate synthetase (alg8), GDP-mannose dehydrogenase (algD), and alginate lyase (algL) genes in multiple drug-resistant (MDR) P. aeruginosa strains. The biofilm formation potential and the expression of alg8, algD, and algL among the bacteria treated with ibuprofen (at sub-inhibitory concentration) were investigated using the crystal violet staining and real-time PCR assays, respectively. The minimum inhibitory concentration of ibuprofen for the studied strains was determined 1024-2048 μg/mL. We observed that ibuprofen was able to reduce bacterial biofilm by 51-77%. Also, the expression of alg8, algD, and algL decreased by 32, 52, and 48%, respectively. The reduction of the genes responsible for alginate synthesis indicates promising antivirulece potential of ibuprofen to combat P. aeruginosa infection, especially in burns and CF patients. Our findings suggest that ibuprofen could be used to reduce the pathogenicity of P. aeruginosa that could be used in combination with antibiotics to treat drug-resistant infections.
- MeSH
- algináty MeSH
- antibakteriální látky metabolismus farmakologie MeSH
- biofilmy MeSH
- cystická fibróza * mikrobiologie MeSH
- ibuprofen metabolismus farmakologie MeSH
- lidé MeSH
- pseudomonádové infekce * farmakoterapie mikrobiologie MeSH
- Pseudomonas aeruginosa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- analgetika * aplikace a dávkování farmakologie škodlivé účinky MeSH
- bolest farmakoterapie MeSH
- fixní kombinace léků * MeSH
- ibuprofen aplikace a dávkování farmakologie škodlivé účinky MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- paracetamol aplikace a dávkování farmakologie škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
Kombinování analgetik je jednou z běžně využívaných metod v léčbě bolesti. Cílem použití analgetických kombinací je využít různé mechanismy účinku k ovlivnění patofyziologie bolestivého stavu. Díky adici, či dokonce potenciaci analgetického účinku dvou látek je možné použít nižší dávky s menším rizikem nežádoucích účinků. Samozřejmě je nutné kombinovat látky s odlišným mechanismem účinku a pokud možno odlišným spektrem účinků nežádoucích.
Combining analgesics is one of the commonly used methods in the treatment of pain. The goal of using analgesic combinations is to use different mechanisms of action to influence the pathophysiology of the painful condition. Thanks to the addition or even potentiation of the analgesic effect of two substances, it is possible to use lower doses with a lower risk of adverse effects. Of course, it is necessary to combine substances with a different mechanism of action and, if possible, a different spectrum of unwanted effects.
