摘要:

The analgesic effects of the non‐steroidal anti‐Inflammatory drugs (NSAIDs) flunixin and dipyrone were assessed in healthy sheep with no pre‐existing inflammation, and in sheep with a chronic inflammatory lesion, using a mechanical noxious stimulus. Saline and dexamethasone were given as controls. Blood taken from healthy sheep after NSAID administration was assayed for thromboxane B2(TxB2) to compare the ability of these drugs to inhibit cyclo‐oxygenase. Both flunixin and dipyrone produced a small but statistically significant rise in pain thresholds (18% and 21% of maximum possible effect respectively) in the healthy sheep which peaked at 30 min and had returned to pre‐drug values by 2–3 h. In the lame sheep a similar effect occurred but the response was smaller, much more variable and tended to be prolonged. Saline and dexamethasone had no effect on thresholds over 6 h in either group of sheep. The rise in thresholds was prevented by pre‐treatment with naloxone (an opioid antagonist) or attpamezole (an α2‐adrenergic antagonist) in the healthy sheep. Naloxone and atipamezole had no effect on thresholds when given alone to healthy sheep. Both NSAIDs Inhibited the production of TxB2to a similar extent. These results indicate that central mechanisms may be involved in

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00573.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The chiral inversion of 2‐arylpropionic acids occurs in many species. It is a unique reaction specific to this group of drugs. In this study R‐(‐)‐fenoprofen (R‐(‐)‐FPF) was used as a model compound to investigate metabolic chiral inversion in sheep invivoandin vitroand to compare the data with the results obtained in rats. Metabolic inversion in sheep was 80%. The apparent mean values of Km andVmaxof thioester formation were: 392 μm and 2.08 nmol/min/mg in sheep and 500 μm and 22 nmol/min/mg in rats. For hydroxylation, the apparent mean values were Vmax: 0.02 nmol/min/mg in rats and 0.01 nmol/min/mg in sheep. There was no correlation betweenin vitrothioesterification and invivochiral inversion in sheep as compared to rats. In sheep most of the thioester formed underwent inversion (80%) while in rats, where invitrothioesterification was greater,in vivoinversion was less (42%). In consequence, in rats other metabolic pathways for R(‐)‐FPF‐CoA, such as incorporation into triacylglycerols and conjugation with amino acids, may be quantit

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00574.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Using scintillation counting and autoradiographical techniques, the whole‐body distribution in week‐old uninfected chickens of the anticoccidial agent sulphaquinoxaline (SQ) labelled with35S was established at various time intervals after a single oral dose either alone or following continuous in‐feed medication with unlabelled SQ, and after a single intravenous dose. The distribution was also established in chickens infected with the coccidiaEimeria acervulinaor E.tenella, after a single oral dose of radiolabelled SQ administered either alone or following continuous in‐feed medication with unlabelled SQ, as for uninfected chicks. In all uninfected chicks, SQ was rapidly absorbed from the gut and was distributed to all tissues. It appeared at high concentrations in the bile and kidneys 0.5 h after dosing. In chickens that had previously received unlabelled SQ in the diet, a radiolabelled dose maintained steadier tissue concentrations than the sharp rise and fall detected after a single oral dose. Intravenous dosing of uninfected chicks showed that SQ was secreted by the crop, gizzard and caecal epithelia into their lumina. Infection with E.acervulinaor E.tenellacoincided with an overall 3.5‐fold sustained increase of SQ concentration in chick tissues. An updated hypothesis including these new observations for the anticoccidial mode of action of SQ in chickens is

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00575.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Plasma concentrations of febantel and its major metabolites, fenbendazole, oxfen‐dazole and fenbendazole sulphone, were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 100 000 L3 larvae of a benzimidazole (BZ)‐ sensitive or BZ‐resistant strain ofOstertagia circumcinctaor with 75 000 L3 larvae of a BZ‐ sensitiveTrichostrongylus colubriformisstrain. The febantel concentrations were always low, and in only a few samples were higher than the limit of detection. A mean decrease in the area under the curve (AUC) for the three metabolites of 10.2%, 16.4% and 4.9% in lambs infected, respectively, with BZ‐sensitive O.circumcincta, BZ‐resistantO. circumcinctaandT. colubriformiswas observed. TheCmaxfor all the metabolites was higher in the BZ‐sensitive O.circumcinctagroup than in the naive sheep, while theTmaxoccurred earlier. TheCmaxand theTmaxvalues for all the metabolites were lower in the BZ‐resistant O.circumcinctagroup than in their own naive controls. In the T.colubriformisgroup the Cmaxvalues of the metabolites were lower and the Tmaxoccu

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00576.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetlc properties of a single intravenous dose of ketoprofen (2.2 mg/kg) in plasma and synovial fluid were compared in four healthy animals and four horses with experimentally induced acute synovitis. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint Ketoprofen was administered at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two‐compartment model in most horses. The plasma harmonic mean half‐life in healthy horses (0.88 h) was longer than in horses with synovitis (0.5 5 h). Synovial fluid concentrations of ketoprofen in healthy horses approximated those in plasma by 3 h post‐dose. In horses with synovitis, synovial fluid concentrations approximated plasma concentrations by 1 h. Synovial fluid concentrations of ketoprofen in horses with synovitis were 6.5 times higher than those in healthy horses at 1 h. The area under the synovial fluid concentration curve for horses with synovitis was greater than in healthy horses. These data suggest that the inflamed joint serves as a site of sequestration for ketoprofen. Furthermore, these results indicate that plasma pharmacokinetics may be altered by inflammation in a peripheral compartment such as the

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00577.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The comparative plasma disposition kinetics of albendazole (ABZ), fenbendazole (FBZ) and oxfendazole (OFZ) following their oral administration (5 mg/kg) to adult sheep was characterized. Jugular blood samples were taken serially over a 144 h period and plasma was analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) (ABZ treatment), and for FBZ, OFZ and FBZ sulphone (FBZSO2) (FBZ and OFZ treatments). While the ABZ parent drug was not detected at any time post‐treatment, ABZSO and ABZSO2were the analytes recovered in plasma, after oral administration of ABZ to sheep. The active ABZSO metabolite was the main analyte recovered in plasma (between 0.25 and 60h post‐treatment), accounting for 71 % of the totalAUC. FBZ, OFZ and FBZSO2were the analytes detected in plasma following the oral administration of both FBZ and OFZ to sheep. Low concentrations of FBZ were found in plasma between 4 (FBZ treatment) or 8 h (OFZ treatment) and 72 h post‐treatment. The plasma profile of each analyte followed a similar pattern after both treatments; OFZ being the main component detected in plasma. The plasma disposition of ABZ metabolites was markedly different to that of FBZ derivatives. ABZSO exhibited faster absorption and a higherCmaxthan OFZ (both treatments). Furthermore, while ABZSO declined relatively rapidly in plasma reaching non‐detectable concentrations at 60 h post‐ABZ administration, OFZ was found in plasma for up to 120 (FBZ treatment) and 144 h (OFZ treatment). The extended detection of OFZ in plasma in both treatments correlated with the prolongedt1/2β(18 h) and mean residence time (MRT) (30–33 h) obtained for this metabolite compared to those of ABZSO (t1/2β= (7.0 h);MRT= 12.5 h). These differences between the disposition of ABZ and FBZ metabolites may account for differences in their patterns of efficacy and ti

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00578.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Vascular leakage induced by intradermal injection of endotoxin, zymosan‐activated plasma (ZAP) and platelet‐activating factor (PAF) was measured in nine Thoroughbreds using 125‐iodine human serum albumin (125I‐HSA) as a marker in the blood. ZAP and PAF produced dose‐dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose‐dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of endotoxin for up to 5 days. However, sites injected with endotoxin and re‐injected with either ZAP or PAF remained responsive with increased vascular leakage compared to saline injected control sites re‐injected with either ZAP or PAF. Diminished response to endotoxin challenge may contribute to the poor prognosis of endotoxaem

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00579.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Amitraz and its active metabolite BTS2 7271 were given intravenously to ponies and sheep at equimolar doses of 1 mg/kg and 0.68 mg/kg, respectively, and the plasma concentrations of amitraz and BTS27271 estimated at various times thereafter. Amitraz was hydrolysed to BTS2 7271 in both species. Amitraz was undetectable in sheep plasma after approximately 5 min but persisted in the plasma of ponies for at least 90 min. The persistence of unmetabolized amitraz in ponies may have implications for the toxicity of amitraz in that species. The primary and secondary disposition half‐lives of amitraz in ponies were 2 and 39 min, respectively. BTS27271 was distributed rapidly outside the plasma in both species with a primary disposition half‐life of 4.4 min in sheep and 5.9 min in ponies. The secondary disposition half‐lives were 51 and 55 min, respectively. The secondary phase of the disposition of BTS27271 was similar whether BTS27271 was given directly or derived by hydrolysis from amitraz. However, significant differences were evident in the primary phase of the disposition of BTS27271. Sheep demonstrated a larger apparent volume of distribution of BTS27271 than ponies and more rapid body clea

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00580.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The effect of xylazine on the isolated sheep trachea and its possible interactions with the α2‐adrenergic antagonist, atipamezole, and the anticholinergic agent, atropine, was studied. The mechanical responses of the tracheal preparations were recorded after exposing each one to cumulatively increasing concentrations of xylazine alone or in the presence of atipamezole or atropine.Xylazine exerted a concentration‐dependent contractile effect, with a threshold concentration of 10‐‐7M while the maximum activity was produced at a concentration of 10‐‐5M (EC50= 2.3 × 10‐‐7). This xylazine‐induced contractile effect was inhibited by atipamezole, but not significantly modified by atropine. Thus, it is concluded that α2‐adrenoceptors exist in the sheep trachea and it is suggested that α2‐adrenoceptor agonists may act on airways in sheep directly through stimulation of peripheral α2‐adrenergic receptors and indirectly via central α2‐adrenergic receptor act

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00581.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration‐time graph was characteristic of a two‐compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with atmaxof 1.46 ± 0.06 h. The elimination half‐life (t1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post‐administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half‐lives of both distribution and elimination phases (t1/2α,t1/2β) and apparent volume of distribution (Vd(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 a

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1995.tb00582.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY