Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat

V. Granados-Soto, J. E. Torres-Löpez, F. J. Flores-Murrieta, J. Pérez-Urizar, F. J. Löpez-Munoz, G. Castaneda-Hernändez

Research output: Contribution to journalArticle

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% 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.
Original languageAmerican English
Pages (from-to)96
Number of pages1
JournalProceedings of the Western Pharmacology Society
StatePublished - 1 Dec 1996
Externally publishedYes

Fingerprint

Diclofenac
Extremities
Intra-Articular Injections
Synovial Fluid
Uric Acid
Knee
Pain
Injections

Cite this

Granados-Soto, V., Torres-Löpez, J. E., Flores-Murrieta, F. J., Pérez-Urizar, J., Löpez-Munoz, F. J., & Castaneda-Hernändez, G. (1996). Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat. Proceedings of the Western Pharmacology Society, 96.
Granados-Soto, V. ; Torres-Löpez, J. E. ; Flores-Murrieta, F. J. ; Pérez-Urizar, J. ; Löpez-Munoz, F. J. ; Castaneda-Hernändez, G. / Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat. In: Proceedings of the Western Pharmacology Society. 1996 ; pp. 96.
@article{d4660546313848d3a2a37288ffbffa97,
title = "Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat",
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{\%} 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.",
author = "V. Granados-Soto and Torres-L{\"o}pez, {J. E.} and Flores-Murrieta, {F. J.} and J. P{\'e}rez-Urizar and L{\"o}pez-Munoz, {F. J.} and G. Castaneda-Hern{\"a}ndez",
year = "1996",
month = "12",
day = "1",
language = "American English",
pages = "96",
journal = "Proceedings of the Western Pharmacology Society",
issn = "0083-8969",
publisher = "Western Pharmacology Society",

}

Granados-Soto, V, Torres-Löpez, JE, Flores-Murrieta, FJ, Pérez-Urizar, J, Löpez-Munoz, FJ & Castaneda-Hernändez, G 1996, 'Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat', Proceedings of the Western Pharmacology Society, pp. 96.

Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat. / Granados-Soto, V.; Torres-Löpez, J. E.; Flores-Murrieta, F. J.; Pérez-Urizar, J.; Löpez-Munoz, F. J.; Castaneda-Hernändez, G.

In: Proceedings of the Western Pharmacology Society, 01.12.1996, p. 96.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat

AU - Granados-Soto, V.

AU - Torres-Löpez, J. E.

AU - Flores-Murrieta, F. J.

AU - Pérez-Urizar, J.

AU - Löpez-Munoz, F. J.

AU - Castaneda-Hernändez, G.

PY - 1996/12/1

Y1 - 1996/12/1

N2 - 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% 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.

AB - 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% 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33748190376&origin=inward

UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=33748190376&origin=inward

M3 - Article

SP - 96

JO - Proceedings of the Western Pharmacology Society

JF - Proceedings of the Western Pharmacology Society

SN - 0083-8969

ER -

Granados-Soto V, Torres-Löpez JE, Flores-Murrieta FJ, Pérez-Urizar J, Löpez-Munoz FJ, Castaneda-Hernändez G. Relationship between blood concentrations and the antinociceptive effect of diclofenac in the rat. Proceedings of the Western Pharmacology Society. 1996 Dec 1;96.