Ketoprofen, 2-(3-benzoylphenyl)-propionic acid, a widely used non-steroidal anti-inflammatory drug, is considered as an important water pollutant. Kinetics and mechanism of its photolytic transformation in aqueous solutions was studied experimentally and partial reaction steps were modelled by means of quantum chemistry methods. While the rate of ketoprofen photolysis was not significantly affected by its acid-base equilibrium, a marked influence of pH on the subsequent degradation reactions was observed. At pH 1.3, two oxygenated primary products were identified, that underwent fast photolysis. Deprotonated form of ketoprofen was transformed preferentially to ethylbenzophenone and further degradation proceeded substantially slower. Oxygen participated on photolytic processes both as a reactant and the triplet state quencher. The active involvement of water molecules in the reaction mechanism was investigated by comparative experiments in acetonitrile. The phototransformation mechanism proposed based on the experimental data corresponded well with the theoretical results.
In this paper we determine acid dissociation constants, limiting ionic mobilities, complexation constants with β-cyclodextrin or heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, and mobilities of resulting complexes of profens, using capillary zone electrophoresis and affinity capillary electrophoresis. Complexation parameters are determined for both neutral and fully charged forms of profens and further corrected for actual ionic strength and variable viscosity in order to obtain thermodynamic values of complexation constants. The accuracy of obtained complexation parameters is verified by multidimensional nonlinear regression of affinity capillary electrophoretic data, which provides the acid dissociation and complexation parameters within one set of measurements, and by NMR technique. A good agreement among all discussed methods was obtained. Determined complexation parameters were used as input parameters for simulations of electrophoretic separation of profens by Simul 5 Complex. An excellent agreement of experimental and simulated results was achieved in terms of positions, shapes, and amplitudes of analyte peaks, confirming the applicability of Simul 5 Complex to complex systems, and accuracy of obtained physical-chemical constants. Simultaneously, we were able to demonstrate the influence of electromigration dispersion on the separation efficiency, which is not possible using the common theoretical approaches, and predict the electromigration order reversals of profen peaks. We have shown that determined acid dissociation and complexation parameters in combination with tool Simul 5 Complex software can be used for optimization of separation conditions in capillary electrophoresis.
- MeSH
- antiflogistika nesteroidní chemie MeSH
- beta-cyklodextriny chemie MeSH
- elektroforéza kapilární metody MeSH
- flurbiprofen chemie MeSH
- ibuprofen chemie MeSH
- ketoprofen chemie MeSH
- koncentrace vodíkových iontů MeSH
- magnetická rezonanční spektroskopie MeSH
- naproxen chemie MeSH
- osmolární koncentrace MeSH
- počítačová simulace MeSH
- software MeSH
- termodynamika MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Dexketoprofen je nesteroidní protizánětlivé léčivo (NSAID) ze skupiny derivátu kyseliny propionové, jedná se o S-(+)-stereoizomer ketoprofenu. Mechanismem účinku je inhibice cyklooxygenázové aktivity prostaglandin H2-syntázy, ze které vyplývají analgetické, antiflogistické a antipyretické účinky dexketoprofenu. S(+)-izomer ketoprofenu (dexketoprofen) je asi 30krát silnější inhibitor COX-1 a asi 100krát silnější inhibitor COX-2. Jeho hlavní výhodou je rychlý nástup účinku (tmax = 0,25–0,75 h). V klinických studiích byla účinnost dexketoprofenu ověřována v terapii muskuloskeletální, pooperační, kolikovité a nádorové bolesti, bolestí hlavy a dysmenorey. Dexketoprofen patří mezi velmi dobře snášená léčiva, podobně jako u ostatních nesteroidních antirevmatik je nejvýraznějším rizikem poškození gastrointestinálního traktu, při krátkodobém podávání je však minimální.
Dexketoprofen is a non-steroid anti-inflammatory drug (NSAID) which is one of propionic acid derivatives – it is the S-(+) stereoisomer of ketoprofen. Its mode of action is the inhibition of the prostaglandin H 2 - synthetase cyclooxygenase activity, from which the analgesic, antiphlogistic and antipyretic effects issue. S(+)-isomer of ketoprofen (dexketoprofen) is an inhibitor of COX-1 which is approximately 30 times stronger and which inhibits COX-2 approximately 100 times more strongly. Its major benefit is the rapid onset of its effect (t max = 0.25–0.75 hour). The efficacy of dexketoprofen was tested in clinical studies in the therapy of musculoskeletal and postoperative pains, colonalgias, cephalalgias and pains caused by tumors and dysmenorrhea. Dexketoprofen is very well tolerated, but – same as with the other non-steroid antirrheumatic drugs – there exists the risk of gastrointestinal damage, which, however, is minimal in the case of a short-term administration.
- Klíčová slova
- DEXOKET,
- MeSH
- antiflogistika nesteroidní farmakologie chemie terapeutické užití MeSH
- antirevmatika farmakologie chemie terapeutické užití MeSH
- bolest farmakoterapie MeSH
- hodnocení léčiv MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- ketoprofen farmakologie chemie terapeutické užití MeSH
- lidé MeSH
- stereoizomerie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
