Pharmacokinetics and pharmacodynamics of anti-infective and anti-inflammatory drugs in animals

In 2 volsAvailable from British Library Document Supply Centre-DSC:DXN052234 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships

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 μg/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

The pharmacokinetics of flunixin meglumine in the sheep

Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t1/2 pi = 2.3 min), a slow body clearance rate (Clb = 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t1/2 pi = 2.7 min, has a slow body clearance rate (Clb = 0.7 ml/kg/min) and an elimination half-life of 205 min. Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration (Cmax) of > or = 5.9 micrograms/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route.Peer reviewe

Bioavailability of different benzimidazole volume-dose formulations in sheep

This article discusses bioavailability of different benzimidazole volume-dose formulations in sheep

Comparison of 2 techniques used for the recovery of nematode infective larvae from pasture

The recovery of gastrointestinal nematode infective larvae from herbage collected manually was compared with the recovery from herbage ingested by sheep with oesophageal fistulae, on five occasions during the grazing season. At least three times more larvae were recovered from the oesophageal fistulates than by manual collection. There was no significant variation between the numbers of larvae collected at 09.00, 12.00 and 15.00, nor was there any difference in the distribution of genera recovered by the two methods. The worm burdens of tracer lambs and the larval counts from the fistulated sheep were used to estimate the rate of larval establishment

Serum thromboxane generation by platelets in several domestic animal species

Blood collected from calves, sheep, goats, pigs, dogs, horses, ponies and donkeys, was allowed to clot under standard conditions. Thromboxane B2 generated during the clotting process was measured by radioimmunoassay in serum harvested from each sample. Highly significant differences were found between species and also between genera within a species. Highest concentrations of thromboxane B2 were detected in the dog samples (887.7 +/- 123.7 ng/ml) and lowest concentrations in samples from sheep (2.7 +/- 0.2 ng/ml). The amount of thromboxane produced per unit number of circulating platelets or per unit volume of platelets in each species was not the same and it would appear that platelets from each species have different inherent ability to produce thromboxane under the stimulus applied, or that some species generate thromboxane from other sources during the clotting process.Peer reviewe