Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats
| Autor: | Luis Alfonso Moreno-Rocha, Adriana Miriam Domínguez-Ramírez, José Raúl Medina-López, Francisco Javier López-Muñoz, Patricia Esmeralda Carrillo-Calzadilla, Alma Rosa Cortés-Arroyo |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Functional impairment Dipyrone Pharmaceutical Science Pain Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Medicine Animals Rats Wistar Active metabolite Pain Measurement Analgesics Dose-Response Relationship Drug Morphine business.industry Long-term potentiation Drug Synergism Drug Tolerance Rats Analgesics Opioid Nociception Pharmacodynamics Drug Therapy Combination business 030217 neurology & neurosurgery medicine.drug Co administration |
| Zdroj: | The Journal of pharmacy and pharmacology. 69(6) |
| ISSN: | 2042-7158 |
| Popis: | Objective To investigate the relationship between metamizol pharmacokinetics and the antinociceptive effect produced after subcutaneous administration of metamizol (177.8 mg/kg) alone or in combination with morphine (3.2 mg/kg), under acute and chronic treatments. Methods Antinociception was assessed using the pain-induced functional impairment model in rat (PIFIR). Serial blood samples were collected from the same animals to study the pharmacokinetics of metamizol. Key findings The co-administration of the drugs in single dose, confirmed the potentiation of their individual antinociceptive effects. When the drugs were administered alone following the chronic schedule, a pronounced tolerance development to their antinociceptive effects was found, whereas it was significantly attenuated when they were administered together. Metamizol pharmacokinetics was unaltered by the presence of morphine. Plasma concentrations of 4-methylaminoantipyrine, an active metabolite markedly decreased under chronic administration. Conclusions The mechanism involved in the potentiation of the antinociceptive effect produced by the combination, cannot be explained by the interaction of morphine on metamizol pharmacokinetics. Other pharmacokinetic interactions along with known pharmacodynamic interactions in which metamizol active metabolites contribute, should be considered. The frequency of administration enhances tolerance development and induces metamizol elimination process. |
| Databáze: | OpenAIRE |
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