• Klíčová slova
• analgetická účinnost, kombinace analgetik,
• MeSH
• antiflogistika nesteroidní MeSH
• farmakoterapie statistika a číselné údaje   MeSH
• financování organizované MeSH
• inhibitory cyklooxygenasy 2 MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• neopioidní analgetika terapeutické užití   MeSH
• preklinické hodnocení léčiv metody   statistika a číselné údaje   MeSH
• statistika jako téma MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH

OBJECTIVES: Paracetamol is converted to an active metabolite AM404 via fatty acid amide hydrolase (FAAH). The aim of the present study was to ascertain whether a FAAH inhibitor URB597 antagonizes paracetamol analgesic activity (and to asses by this way the role of FAAH in analgesic activity of paracetamol). METHODS: The interaction between a FAAH inhibitor URB597 and paracetamol was investigated in the writhing test in mice using an isobolographic analysis. RESULTS: URB597 or paracetamol alone and in combinations produced dose-dependent antinociceptive effects. ED50 values were estimated for the individual drugs and an isobologram was constructed. The observed ED50 value for the URB57-paracetamol combination was 0.097 (0.062-0.247) mg/kg. This value did not differ significantly from the theoretical additive ED50 value for the URB597-paracetamol combination which was 0.108 (0.059-0.198) mg/kg. Thus, inhibition of FAAH by URB597 was not followed by the lack of analgesic activity in paracetamol. CONCLUSION: The present results suggest that the analgesic activity of paracetamol is not dependent solely on FAAH metabolic conversion to AM404 and that paracetamol exerts analgesic activity also by additional mechanisms.

• MeSH
• amidohydrolasy antagonisté a inhibitory   MeSH
• benzamidy farmakologie   MeSH
• karbamáty farmakologie   MeSH
• lékové interakce MeSH
• lineární modely MeSH
• měření bolesti účinky léků   MeSH
• myši MeSH
• neopioidní analgetika farmakologie   MeSH
• paracetamol farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim of the study was to ascertain whether rilmenidine, a second generation imidazoline-alpha-2-adrenoreceptor agonist, is able to increase analgesic effects of ibuprofen in the writhing test in mice. Experimental studies combining these agents have not yet been published. METHODS: An acetic acid (0.7%) solution was injected into the peritoneal cavity and the number of writhes was counted. The influence on locomotor performance was tested using the rotarod test. RESULTS: Rilmenidine, ibuprofen, and rilmenidine-ibuprofen fixed-ratio combinations produced dose-dependent antinociceptive effects. ED50 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical additive ED50 value for the rilmenidine-ibuprofen combination was 34.00 +/- 9.39 mg/kg. This value was significantly greater than the observed ED50 value which was 18.07 +/- 5.41 mg/kg, indicating a synergistic interaction. Rilmenidine did not impair motor coordination, as measured by the rotarod test, at antinociceptive and higher doses. CONCLUSIONS: The present results suggest that rilmenidine enhances the analgesic activity of ibuprofen. If rilmenidine produces antinociception in humans, then the synergistic antinociception of rilmenidine with ibuprofen could offer therapeutic advantage for clinical treatment of pain.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   MeSH
• analýza rozptylu MeSH
• bolest farmakoterapie   chemicky indukované   MeSH
• ibuprofen farmakologie   MeSH
• kyselina octová MeSH
• měření bolesti MeSH
• metoda rotující tyčky MeSH
• myši MeSH
• neopioidní analgetika farmakologie   MeSH
• oxazoly farmakologie   MeSH
• pohybová aktivita účinky léků   MeSH
• synergismus léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

CE with contactless conductivity detection has been used to determine the glycine neurotransmitter in periaqueductal gray matter (PAG) of rats. The LOD for glycine has been decreased to a value of 0.2 microM by adding 75% v/v of ACN to the samples and increasing the sample zone introduced to a value of 20% of the overall capillary length. The repeatabilities of the analyte migration times and the zone areas amount to 2.1 and 2.7%, respectively. The optimized CE/contactless conductivity detection method makes it possible to determine the micromolar concentrations of glycine in PAG microdialyzates without the necessity of sample derivatization. It follows from a pharmacological study that a local inflammation initiated by an application of carrageenan increased the glycine concentration in the rat PAG seven times, compared with a control. The glycine level in PAG can be decreased and the pain suppressed by administering paracetamol.

• MeSH
• bolest farmakoterapie   chemicky indukované   MeSH
• elektrická vodivost MeSH
• elektroforéza kapilární metody   MeSH
• glycin analýza   metabolismus   MeSH
• karagenan farmakologie   MeSH
• krysa rodu rattus MeSH
• neopioidní analgetika farmakologie   MeSH
• paracetamol farmakologie   MeSH
• potkani Wistar MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• substantia grisea centralis chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• analgetika diagnostické užití   farmakologie   MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• ibuprofen farmakologie   MeSH
• imidazoly antagonisté a inhibitory   diagnostické užití   farmakologie   MeSH
• měření bolesti metody   využití   MeSH
• myši MeSH
• oxazoly diagnostické užití   farmakologie   MeSH
• paracetamol farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• abstrakty MeSH

Although benzimidazole anthelmintic flubendazole, methyl ester of [5-(4-fluorobenzoyl)-1H-benzimidazol-2-yl]carbamic acid, is extensively used in veterinary and human medicine for the treatment of gastrointestinal parasitic helminth infections, reliable data about its pharmacokinetics in various species have not been reported. Our previous work [M. Nobilis, Th. Jira, M. Lisa, M. Holcapek, B. Szotakova, J. Lamka, L.Skalova, J. Chromatogr. A 1149 (2007) 112-120] had described the stereospecificity of carbonyl reduction during phase I metabolic experiments in vitro. For in vivo pharmacokinetic studies, further improvement and optimization of bioanalytical HPLC method in terms of sensitivity and selectivity was necessary. Hence, a modified chiral bioanalytical HPLC method involving both UV photodiode-array and fluorescence detection for the determination of flubendazole, both enantiomers of reduced flubendazole and hydrolyzed flubendazole in the extracts from plasma samples was tested and validated. Albendazole was used as an internal standard. Sample preparation process involved a pH-dependent extraction of the analytes from the blood plasma into tert-butylmethyl ether. Chromatographic separations were performed on a Chiralcel OD-R 250 mm x 4.6mm column with mobile phase methanol-1M NaClO(4) (75:25, v/v) at the flow rate 0.5 ml min(-1). In quantitation, selective UV absorption maxima of 290 nm (for reduced flubendazole), 295 nm (for albendazole), 310 nm (for flubendazole) and 330 nm (for hydrolyzed flubendazole) were used in the UV photodiode-array detection, and lambda(exc.)/lambda(emis.)=228 nm/310 nm (for reduced flubendazole) and lambda(exc.)/lambda(emis.)=236 nm/346 nm (for albendazole) were set on the fluorescence detector. The fluorescence detection was approximately 10-times more sensitive than the UV detection. Each HPLC run lasted 27 min. The validated chiral HPLC-PDA-FL method was employed in the pharmacokinetic studies of flubendazole in sheep. The stereospecificity of the enzymatic carbonyl reduction of flubendazole was also observed in vivo. (+)-Reduced flubendazole was found to be the principal metabolite in ovine blood plasma and only low concentrations of hydrolyzed flubendazole, the parent flubendazole and (-)-reduced flubendazole were detected in this biomatrix.

• MeSH
• anthelmintika farmakokinetika   krev   MeSH
• fluorescenční spektrometrie MeSH
• mebendazol analogy a deriváty   farmakokinetika   krev   MeSH
• ovce domácí MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• spektrofotometrie ultrafialová MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• validační studie MeSH

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• C-reaktivní protein účinky léků   MeSH
• cyklooxygenasa 1 účinky léků   MeSH
• cyklooxygenasa 2 účinky léků   MeSH
• cystická fibróza farmakoterapie   MeSH
• dítě MeSH
• farmakologické účinky MeSH
• ibuprofen aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• léky bez předpisu aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• nemoci úst farmakoterapie   MeSH
• osteoartróza farmakoterapie   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH