Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation.

Article Details

Citation

Copy to clipboard

Lees P, McKellar QA, Foot R, Gettinby G

Pharmacodynamics and pharmacokinetics of tolfenamic acid in ruminating calves: evaluation in models of acute inflammation.

Vet J. 1998 May;155(3):275-88.

PubMed ID

9638074 [ View in PubMed

]

Abstract

Injections of mild irritants intradermally (carrageenan, zymosan and dextran) and intracaveally (carrageenan) in a tissue cage model of inflammation were used in studies of the pharmacodynamics and pharmacokinetics of tolfenamic acid administered intramuscularly in calves. Inhibition of serum thromboxane (TX)B2 and inflammatory exudate prostaglandin (PG)E2 were used as indicators of the magnitude and time course of blockade of cyclo-oxygenase isoforms COX-1 and COX-2, respectively. Single doses of 2, 4 and 8 mgkg-1 tolfenamic acid partially inhibited irritant-induced rises in skin temperature (non-dose dependently) and skin oedema (dose-dependently). These doses also markedly inhibited serum TXB2 synthesis and the duration of inhibition was dose-related. A dose of 2 mgkg-1 tolfenamic acid also attenuated skin temperature rise over carrageenan-injected tissue cages, and markedly inhibited exudate PGE2 synthesis, even though drug penetration into both exudate and tissue cage transudate was limited. Tolfenamic acid pharmacokinetics were characterized by a relatively short tmax (0.94-2.04 h), a high estimated Vdarea (1.79-3.20 Lkg-1), an estimated t1/2 beta of 8.01-13.50 h and Cl beta of 0.142-0.175 Lkg-1h-1. The actions of tolfenamic acid in inhibiting PGE2 synthesis and in attenuating two of the cardinal signs of inflammation (heat and swelling) suggest that a dosage of 2 mgkg-1 administered intramuscularly should be effective clinically as an anti-inflammatory agent.

DrugBank Data that Cites this Article

Drugs

Tolfenamic acid

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tolfenamic acid	Prostaglandin G/H synthase 1	Protein	Humans	Yes	Antagonist	Details
Tolfenamic acid	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Antagonist	Details