Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats

Pharmacological characteristics of metamizole

“…This is also true for metamizole, as it has been proven that co-administration of metamizole with morphine (López-Muñ oz et al 2008, Domtnguez-Ramtrez et al 2010, paracetamol or ketoprofen (Oberhofer et al 2005) is able to produce potentiation of antinociceptive effects. Domínguez-Ramírez et al (2010) demonstrated that co-administration of morphine and metamizole under acute treatment produced a significantly higher antinociceptive effect than that obtained with morphine alone. Interestingly, simultaneous administration of both drugs caused a nearly triple increase in the C max of morphine, which was most likely caused by the enzymatic inhibition of the glucuronosyl-transferase system involved in the metabolism of morphine.…”

“…Interestingly, simultaneous administration of both drugs caused a nearly triple increase in the C max of morphine, which was most likely caused by the enzymatic inhibition of the glucuronosyl-transferase system involved in the metabolism of morphine. Domínguez-Ramírez et al (2010) claim that the discussed effect was caused by mutual competition of both drugs for the same enzymatic mechanism of their metabolism. Thus, most probably the potentiation of morphine antinociception by metamizole originates not only from the interaction at the pharmacodynamic level, but also from the modification of the pharmacokinetics of morphine.…”

Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats

“…Previously, it was demonstrated that the antinociceptive effect of the combination of morphine (MOR) and metamizol (MET), 5.6 + 562.3 mg/kg s.c. respectively, was significantly higher than that observed with the drugs administered individually at the same doses in arthritic rats, either after single or chronic treatments . In this case, the pharmacodynamic mechanism for the interaction between MOR and MET was partially attributed to opioidergic system participation .…”

“…Other mechanisms such as the l ‐arginine‐NO‐cyclic GMP pathway and interaction with N ‐methyl d ‐aspartic acid receptors were proposed to explain the synergism and the delay in the development of tolerance observed with the combination of such drugs. Additionally, a pharmacokinetic interaction between MET (562.3 mg/kg, s.c.) and MOR (5.6 mg/kg, s.c.) that leads to an increased antinociceptive effect and a delay on the tolerance development was also demonstrated . While plasma concentrations of MOR markedly diminished after subchronic administration of the drug alone, the simultaneous administration with MET in a single and multiple dosing (1 dose/day/6 or 12 days) produced an increase of MOR C max and AUC ( P < 0.001).…”

“…Treatment to relieve acute and chronic pain requires the use of strong analgesic drugs; among them the opioid compounds have a high efficacy against severe pain when they are administered in single dose. However, the usefulness of these drugs in treating chronic pain is limited because of the development of tolerance to the analgesic effect after repeated administrations, which results in a gradual escalation of the administered dose and therefore an increased incidence of its adverse effects …”