abstract

• The blood levels and antinociceptive effect of diclofenac were investigated in the rat. Pain was induced by the intraarticular injection of 0.05 ml of 30%25 uric acid in the knee of the right hind limb, and was evaluated as the dysfunction produced considering the left hind limb as control. 2 h after injection, rats received diclofenac (0.56, 1, 1.8, 3.2, 5.6 and 10 mg/kg; po) and the recovery of the functionality was considered as the antinociceptive effect. The antinociceptive effect and the blood level were determined simultaneously at selected times for the next 6 h. The blood level increased in a dose-dependent manner, which was reflected as an increase in the antinociceptive effect. However, when the antinociceptive effect was plotted as function of blood level, a counterclockwise hysteresis loop was observed for all doses. Hysteresis collapse was achieved by calculating the concentration in the effect compartment (Ce) and relating it with the antinociceptive effect. The relationship between Ce and the antinociceptive effect was well fitted by the sigmoidal Emax model (r 0.90) with a K of 0.1227 hr1. Our results suggest that the delay between the antinociceptive effect and the blood level could be due to the accumulation of diclofenac in synovial fluid. This could explain why the antinociceptive effect lasts longer than expected from the blood level.
• The blood levels and antinociceptive effect of diclofenac were investigated in the rat. Pain was induced by the intraarticular injection of 0.05 ml of 30%25 uric acid in the knee of the right hind limb, and was evaluated as the dysfunction produced considering the left hind limb as control. 2 h after injection, rats received diclofenac (0.56, 1, 1.8, 3.2, 5.6 and 10 mg/kg; po) and the recovery of the functionality was considered as the antinociceptive effect. The antinociceptive effect and the blood level were determined simultaneously at selected times for the next 6 h. The blood level increased in a dose-dependent manner, which was reflected as an increase in the antinociceptive effect. However, when the antinociceptive effect was plotted as function of blood level, a counterclockwise hysteresis loop was observed for all doses. Hysteresis collapse was achieved by calculating the concentration in the effect compartment (Ce) and relating it with the antinociceptive effect. The relationship between Ce and the antinociceptive effect was well fitted by the sigmoidal Emax model (r 0.90) with a K%2b of 0.1227 hr1. Our results suggest that the delay between the antinociceptive effect and the blood level could be due to the accumulation of diclofenac in synovial fluid. This could explain why the antinociceptive effect lasts longer than expected from the blood level.

authors

• Castañeda-Hernández G.
• Flores-Murrieta F.J.
• Granados-Soto V.
• Löpez-Munoz F.J.
• Pérez-Urizar J.
• Torres-Löpez J.E.

publication date

• 1996-01-01

published in

• Proceedings of the Western Pharmacology Society  Journal

start page

• 96

end page

volume

• 39