RESUMO
In order to evaluate the pharmacokinetics of metamizol in the presence of morphine in arthritic rats, after subcutaneous administration of the drugs, an easy, rapid, sensitive and selective analytical method was proposed and validated. The four main metamizol metabolites (4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine) were extracted from plasma samples (50-100µl) by a single solid-phase extraction method prior to reverse-phase high performance liquid chromatography with diode-array detection. Standard calibration graphs for all metabolites were linear within a range of 1-100µg/ml (r(2)≥0.99). The intra-day coefficients of variation (CV) were in the range of 1.3-8.4% and the inter-day CV ranged from 1.5 to 8.4%. The intra-day assay accuracy was in the range of 0.6-9.6% and the inter-day assay accuracy ranged from 0.9 to 7.5% of relative error. The lower limit of quantification was 1µg/ml for all metabolites using a plasma sample of 100µl. Plasma samples were stable at least for 4 weeks at -20°C. This method was found to be suitable for studying metamizol metabolites pharmacokinetics in arthritic rats, after simultaneous administration of metamizol and morphine, in single dose.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dipirona/sangue , Dipirona/farmacocinética , Morfina/farmacologia , Aminopirina/análogos & derivados , Aminopirina/sangue , Aminopirina/química , Ampirona/análogos & derivados , Ampirona/sangue , Ampirona/química , Animais , Calibragem , Cromatografia de Fase Reversa/métodos , Dipirona/análogos & derivados , Dipirona/química , Interações Medicamentosas , Masculino , Ratos , Ratos Wistar , Extração em Fase Sólida/métodosRESUMO
BACKGROUND: The antinociceptive effects of metamizol and morphine administered either separately or in combination were determined in the "Pain-Induced Functional Impairment Model in the Rat" (PIFIR antinociceptive model). METHODS: Intense nociception (or intense pain) was induced by the intra-articular injection of uric acid (50%) in the right hind limb inducing its dysfunction. Animals then received analgesic agents, and the recovery of functionality over time was assessed as an expression of antinociception. RESULTS: Metamizol (177.8 mg/kg s.c.) or morphine (3.2 mg/kg s.c.) separately resulted in a lower antinociceptive effect (22.1+/-5.4 area units [au] and 31.8+/-9.4 au, respectively). Moreover, the combination of metamizol (177.8 mg/kg) with morphine (3.2 mg/kg) resulted in a potentiation (293.7+/-16.6 au). The antinociceptive effect observed using the combination was significantly greater than expected on the basis of addition of the individual effects. The percent change in antinociceptive effects, using the combination, was 444.9%. CONCLUSIONS: This represents the first study to show that metamizol + morphine can produce potentiation of their antinociceptive effects in intense pain.
Assuntos
Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Dipirona/administração & dosagem , Morfina/administração & dosagem , Dor/tratamento farmacológico , Animais , Artrite Gotosa , Quimioterapia Combinada , Masculino , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Ácido Úrico/administração & dosagemRESUMO
Histochemical and electrochemical studies were carried out on skeletal rat muscles treated with dantrolene sodium (DS) for 60 days. Histochemical experiments revealed a conversion from fast twitch (type II) to slow twitch (type I) fibers for soleus (S), gastrocnemius (GM), and extensor digitorum longus (EDL) muscles. However, a significant decreased of muscle contractility was not observed in these chronically treated rat muscles in opposition to both those directly exposed in vitro as the muscles obtained from only 1-h DS-treated animals