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Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1994 Mar 03; Vol. 253 (3), pp. 191-200. - Publication Year :
- 1994
-
Abstract
- Tolfenamic acid was administered to beagle dogs at 2, 4 and 8 mg/kg bodyweight i.m. and the concentration of drug in plasma and in inflamed (administered carrageenan) and non-inflamed subcutaneous tissue cage fluid was measured. The concentration of thromboxane B2 in serum from blood allowed to clot under standardized conditions was determined and the concentrations of prostaglandin E2, 12-hydroxyeicosatetraenoic acid (12-HETE) and leucocyte numbers were measured in fluid from the carrageenan administered tissue cages. Skin temperature was also measured over each tissue cage following administration of drug. Tolfenamic acid displayed linear pharmacokinetics since the area under the plasma concentration time curve (AUC) values were 13.74 +/- 1.88, 29.82 +/- 6.53 and 50.52 +/- 5.73 micrograms/ml.h following administration of 2, 4 and 8 mg/kg, respectively. Tolfenamic acid proved to be a potent inhibitor of ex vivo thromboxane B2 generation in clotting blood. Maximal inhibition was greater than 80% at all dose rates and 97% at the 8 mg/kg dose rate 1 h after drug administration. It also proved to be a potent inhibitor of prostaglandin E2 production in inflammatory exudate, and significantly (P < 0.05) decreased prostaglandin E2 production at all dose levels. Tolfenamic acid did not significantly alter 12-HETE generation or white blood cell accumulation in inflammatory exudate. Tolfenamic acid significantly reduced the elevated skin temperature over carrageenan administered cages at all dose levels.
- Subjects :
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Animals
Anti-Inflammatory Agents, Non-Steroidal administration & dosage
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Cell Count drug effects
Dinoprostone metabolism
Dogs
Dose-Response Relationship, Drug
Female
Hydroxyeicosatetraenoic Acids metabolism
Inflammation drug therapy
Injections, Intramuscular
Leukocyte Count drug effects
Male
Skin Temperature drug effects
ortho-Aminobenzoates administration & dosage
ortho-Aminobenzoates blood
ortho-Aminobenzoates pharmacology
Anti-Inflammatory Agents, Non-Steroidal pharmacokinetics
Exudates and Transudates metabolism
Inflammation metabolism
Thromboxane B2 blood
ortho-Aminobenzoates pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 253
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 8200415
- Full Text :
- https://doi.org/10.1016/0014-2999(94)90191-0