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R Foot

Publications and source records attributed to R Foot.

At least 19 recordsLinked to original sources
PubMed1998

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

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.

Animals↗
PubMed1996

Pharmacodynamics and chiral pharmacokinetics of carprofen in calves.

The non-steroidal anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 to six Friesian bull calves aged 8-10 weeks. Anti-inflammatory properties were indicated by attenuation of temperature rise at sites of intradermal injection of the irritants, carrageenin and dextran, but responses were not statistically significant at most recording times. Carrageenin- and dextran-induced swelling were not significantly reduced by carprofen. Carprofen reduced ex vivo serum thromboxane B2 synthesis but this effect was also not significant at most sampling times. Enantioselective pharmacokinetics of carprofen was demonstrated, plasma concentrations of the R(-) enantiomer predominating at all sampling times. It is concluded that inhibition of cyclo-oxygenase is unlikely to be the sole mechanism of action of carprofen in calves.

Animals↗
PubMed1996

Evaluation of carprofen in calves using a tissue cage model of inflammation.

The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 body weight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory and pharmacokinetic properties were investigated using a tissue cage model of inflammation based on intracaveal injection of the mild irritant, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring times. Elimination half-life and mean residence time were shorter and volume of distribution and clearance were greater for the S(+) than for the R(-) enantiomer. Penetration of both enantiomers into transudate (non-stimulated tissue cage) was poor but penetration into exudate (carrageenin-stimulated tissue cage) was good. Carprofen failed to reduce exudate concentration of prostaglandin E2 and the reductions in 12-hydroxyeicosatetraenoic acid were non-significant at most sampling times. The long elimination half-life of both R(-) and S(+) carprofen enantiomers and their ready penetration into and slow clearance from inflammatory exudate indicate that the drug is likely to have a long duration of action in calves. The mechanism of action is unknown but it is unlikely to involve inhibition of either cyclooxygenase or 12-lipoxygenase.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat.

The pharmacodynamics and enantioselective pharmacokinetics of the arylpropionic acid non-steroidal anti-inflammatory drug, carprofen, were investigated in cats after administration of the racemic mixture (rac-carprofen) at dose rates ranging from 0.7 to 4.0 mg kg-1 intravenously and subcutaneously. A low dose of rac-carprofen (0.7 mg kg-1) partially inhibited the rise in skin temperature at a site of acute inflammation but had no effect on the ex vivo synthesis of serum thromboxane (Tx) B2. A higher dose (4.0 mg kg-1) inhibited oedematous swelling, although the response was statistically significant at only one time, and also reduced the ex vivo synthesis of serum TxB2 for 12 hours after intravenous injection or 24 hours after subcutaneous injection. The main features of carprofen pharmacokinetics were a low distribution volume, a relatively long elimination half-life, the predominance of the R(-) enantiomer and a bioavailability (after subcutaneous dosing) of 100 per cent and 92 per cent, respectively, after doses of 0.7 and 4.0 mg kg-1. On the basis of these data, it is suggested that a dose of 4.0 mg kg-1 by both intravenous and subcutaneous routes should be evaluated in clinical subjects.

Animals↗
PubMed1996

Effects of flunixin, tolfenamic acid, R(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation.

The objective of this study was to analyse the effects of 4 nonsteroidal anti-inflammatory drugs (NSAIDs) on the production of beta-glucuronidase (beta-glu), tumour necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated equine synoviocytes. The agents studied were flunixin, tolfenamic acid, S(+)ketoprofen (KTP) and R(-)ketoprofen. LPS-induced release of beta-glu from synoviocytes was inhibited in a concentration dependent manner by all 4 compounds, tolfenamic acid being the most potent. Of the 2 KTP enantiomers, S(+)KTP exerted the greatest inhibitory effect. Tolfenamic acid and flunixin increased the production of IL-6-like activity by LPS-stimulated synoviocytes only at the highest concentration studied (1000 mumol/l). Lower concentrations produced no effect on IL-6. Flunixin, tolfenamic acid and S(+)KTP produced statistically significant and concentration related increases in the release of IL-1-like activity by LPS-stimulated synoviocytes. Prostaglandin E2 synthesis was markedly inhibited in a concentration dependent manner by the 4 NSAIDs. However, R(-)KTP was effective only at the highest concentrations investigated (1000 and 100 mumol/l). The present findings are compatible with the possibility that longterm use of NSAIDs in arthropathies, by removing the regulator role of PGE2 on IL-1 synthesis, might enhance the pathological process of cartilage degeneration.

Animals↗
PubMed1994

SU(3)L

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Journal Article↗