The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies.
- MeSH
- chlorpropamid analýza farmakologie MeSH
- diklofenak analýza farmakologie MeSH
- elektroforéza kapilární MeSH
- fenylbutazon analýza farmakologie MeSH
- flurbiprofen analýza farmakologie MeSH
- ibuprofen analýza farmakologie MeSH
- lidé MeSH
- lidokain antagonisté a inhibitory chemie MeSH
- lidský sérový albumin chemie MeSH
- tolbutamid analýza farmakologie MeSH
- tryptofan antagonisté a inhibitory chemie MeSH
- vazebná místa účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Early stages of ontogenesis determining subsequent growth, development, and productivity of crops can be affected by wastewater and sludge contaminated with pharmaceuticals. Diclofenac (DCF) and paracetamol (PCT; both 0.0001 to 10 mg/L) did not affect seed germination and primary root length of onion, lettuce, pea, and tomato. Conversely, 20-day-old pea and maize plants exhibited decrease in biomass production, leaf area (by approx. 40% in pea and 70% in maize under 10 mg/L DCF), or content of photosynthetic pigments (by 10% and 60% under 10 mg/L PCT). Quantum yields of photosystem II were reduced only in maize (FV/FM and ΦII by more than 40% under 10 mg/L of both pharmaceuticals). Contents of H2O2 and superoxide increased in roots of both species (more than four times under 10 mg/L PCT in pea). Activities of antioxidant enzymes were elevated in pea under DCF treatments, but decreased in maize under both pharmaceuticals. Oxidative injury of root cells expressed as lowered oxidoreductase activity (MTT assay, by 40% in pea and 80% in maize) and increase in malondialdehyde content (by 60% and 100%) together with the membrane integrity disruption (higher Evans Blue accumulation, by 100% in pea and 300% in maize) confirmed higher sensitivity of maize as a C4 monocot plant to both pharmaceuticals.
- MeSH
- antioxidancia analýza MeSH
- chemické látky znečišťující vodu toxicita MeSH
- diklofenak analýza toxicita MeSH
- fotosyntéza účinky léků MeSH
- klíčení účinky léků MeSH
- kořeny rostlin účinky léků metabolismus MeSH
- listy rostlin účinky léků MeSH
- malondialdehyd analýza MeSH
- odpadní voda chemie MeSH
- paracetamol analýza toxicita MeSH
- peroxid vodíku analýza metabolismus MeSH
- semena rostlinná účinky léků fyziologie MeSH
- zemědělské plodiny účinky léků růst a vývoj MeSH
- Publikační typ
- časopisecké články MeSH
Non-steroidal anti-inflammatory drugs (NSAIDs) belong to most used pharmaceuticals in the human and veterinary medicine. The widespread consumption of NSAIDs has led to their ubiquitous occurrence in water environment including large river systems. In the present study, concentrations of the five most frequently used NSAIDs (ibuprofen, diclofenac, naproxen, ketoprofen and indomethacin) were determined in the watercourses of the river Elbe basin in Czech Republic. The presence of the pharmaceuticals was measured at 29 sampling sites including urban and rural areas, small creeks and main tributaries of the Elbe monthly from April to December of 2011. For the NSAIDs quantitation, the comprehensive analytical method combing pentafluorobenzyl bromide (PFBBr) derivatization with highly sensitive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) was developed. Although the content of all NSAIDs varied at the particular sampling points significantly, total amount of particular compounds was relatively stable during all monitored periods with only non-significant increase in the spring and autumnal months. Ibuprofen was found to be the most abundant drug with maximum concentration of 3210 ng/L, followed by naproxen, diclofenac and ketoprofen (1423.8 ng/L, 1080 ng/L and 929.8 ng/L, respectively). Indomethacin was found only at several sampling sites (maximum concentration of 69.3 ng/L). Concentrations of all compounds except ibuprofen were significantly higher at sampling sites with low flow rates (creeks), followed by the biggest watercourses.
- MeSH
- antiflogistika nesteroidní analýza MeSH
- chemické látky znečišťující vodu analýza MeSH
- diklofenak analýza MeSH
- ibuprofen analýza MeSH
- indomethacin analýza MeSH
- ketoprofen analýza MeSH
- monitorování životního prostředí MeSH
- naproxen analýza MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- řeky chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The subject of this work is the definition of a simple model based on general ITP theory that allows describing and predicting the behavior of ITP systems compatible with ESI-MS detection. The model is exemplified by anionic ITP of weak acids that represent an interesting potential application field of ITP-ESI-MS. Suitable ESI-compatible electrolyte systems of very simple composition are proposed including a special free-acid ITP arrangement. The properties of these systems are discussed using illustrative diagrams of their stacking windows. The use of anionic ITP-ESI-MS in negative-ion ESI mode is reported for the first time and its suitability for sensitive trace analysis is demonstrated. The presented ITP-ESI-MS application example comprises a free-acid ITP system formed of formic and propionic acids and direct injection analysis of ibuprofen and diclofenac in waters with quantitation limits of the order 10(-10) M.
- MeSH
- anionty chemie MeSH
- antiflogistika nesteroidní analýza MeSH
- diklofenak analýza MeSH
- elektroforéza kapilární MeSH
- elektrolyty chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- ibuprofen analýza MeSH
- izotachoforéza metody MeSH
- kyseliny chemie MeSH
- limita detekce MeSH
- neopioidní analgetika analýza MeSH
- pitná voda analýza MeSH
- řeky chemie MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- MeSH
- chemické techniky analytické * metody využití MeSH
- diklofenak * analýza MeSH
- farmaceutická technologie MeSH
- indikátory a reagencie MeSH
- lidé MeSH
- metody pro přípravu analytických vzorků MeSH
- neopioidní analgetika MeSH
- odpadní vody * MeSH
- referenční standardy MeSH
- spektrofotometrie ultrafialová * metody přístrojové vybavení využití MeSH
- Check Tag
- lidé MeSH
A new method for the determination of kinetic and inhibition parameters of cytochromes P450 reactions by means of on-line CE was developed. It is based on transverse diffusion of laminar flow profiles methodology introduced by Krylov et al. that injection procedure was modified. The solutions of an enzyme and its substrates are injected by hydrodynamic pressure as a series of repeated consecutive plugs. Proposed injection of three plugs of enzyme surrounded with plugs of substrates represents a certain trade-off to obtain the reaction mixture with the satisfying homogeneity by the short-injection procedure as possible. Mathematical modeling confirmed the assumption of a consistent distribution of reactants in the final reaction mixture. Kinetic and inhibition studies of cytochrome P450 isoform 2C9's reaction with diclofenac as a probe substrate and sulfaphenazole as a probe inhibitor were conducted in order to prove the practical applicability of the proposed method for on-line screenings of drug metabolism mediated by cytochrome P450 enzymes. As a result, an apparent Michaelis constant of 2.66 ± 0.18 μM, apparent maximum reaction velocity of 7.91 ± 0.22 nmol min(-1) nmol(-1) , Hill coefficient of 1.59 ± 0.16, half maximal inhibitory concentration of 0.94 ± 0.04 μM and apparent inhibition constant of 0.39 ± 0.07 μM were determined. All these values are in agreement with literature data obtained using different techniques. In addition, less than 30 nL of cytochrome P450 2C9 solution was consumed per analysis in the kinetic and inhibition studies using this method.
- MeSH
- aromatické hydroxylasy metabolismus MeSH
- chemické modely MeSH
- difuze MeSH
- diklofenak analýza metabolismus MeSH
- elektroforéza kapilární metody MeSH
- enzymatické testy metody MeSH
- kinetika MeSH
- léčivé přípravky analýza metabolismus MeSH
- lidé MeSH
- rekombinantní proteiny metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cílem práce bylo sledování vlivu koncentrace lipofilního nosiče na vlastnosti hydrofilně-lipofilních matricových tablet pro prodloužené uvolňování diklofenaku sodné soli se zaměřením na optimalizaci disolučního profilu v podmínkách in vitro. Lipofilním nosičem byl cetylalkohol, který měl současně funkci tajícího pojiva v procesu termoplastické granulace, povidon se použil jako gelotvorný polymer, plnivem byla sacharosa nebo laktosa. Výsledky ukázaly, že koncentrace cetylalkoholu měla vliv na jakostní parametry granulátů i připravených matricových tablet. Koncentrace cetylalkoholu ovlivňovala disoluční profil sacharosových vzorků statisticky významně, v případě vzorků s obsahem laktosy se výrazně projevila pouze při jeho vyšší koncentraci. S rostoucí koncentrací cetylalkoholu se uvolňování léčiva zpomalovalo; vzorky s obsahem sacharosy uvolňovaly léčivo rychleji ve srovnání s identickými vzorky s obsahem laktosy. Vliv byl výraznější při nižší koncentraci lipofilního nosiče.
The present experimental paper aimed to examine the effect of lipophilic carrier concentration on diclofenac sodium prolonged release from hydrophilic-lipophilic matrix tablets with respect to the optimization of its dissolution profile in vitro. The lipophilic carrier was cetyl alcohol contemporaneously acting as the melting binder in thermoplastic granulation, povidone was used as the gel-forming agent, sucrose or lactose were fillers. The obtained results indicated that cetyl alcohol concentration influenced both characteristics of the granulates and the tablets. The dissolution profile of sucrose samples was affected statistically significantly by cetyl alcohol concentration, in the case of lactose samples only when a higher cetyl alcohol concentration was used. The increasing concentration of cetyl alcohol led to a slower drug release. From the obtained results it is apparent that sucrose samples released drug faster in comparison with the lactose monohydrate ones, especially when a lower lipid carrier concentration was used.
- MeSH
- diklofenak analýza MeSH
- nosiče léků farmakokinetika chemie MeSH
- tablety farmakokinetika klasifikace MeSH
- Publikační typ
- techniky in vitro MeSH
- MeSH
- chromatografie kapalinová metody využití MeSH
- diklofenak analýza MeSH
- indoly analýza MeSH
- parabeny analýza MeSH
- Publikační typ
- techniky in vitro MeSH
