摘要:

The effect of ticlopidine on platelet function, platelet number, mean platelet volume, antithrombin III activity, and fibrinogen was evaluated in 10 laboratory beagles. Ticlopidine (62 mg/kg) significantly inhibited ADP‐ and collagen‐induced platelet aggregation within 2 days of the beginning of oral administration. Collagen‐induced platelet14C‐serotonin release was not inhibited by day 9 of medication but was inhibited by day 20 in two of three beagles given medication for 32 days. Significant increases in mean platelet number were observed on days 2 and 5. The trend toward increased platelet number continued until day 16, at which time platelet number began to decrease toward baseline in three of three dogs treated for 32 days. Mean platelet volume (MPV) was significantly decreased compared to baseline on days 5 and 9. In three dogs treated for 32 clays, the lowest MPV was observed on day 9 in two dogs and on day 12 in one dog. Significant changes were not observed in antithrombin III activity or fibrinogen with ticlopicline tr

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00980.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effect of intraruminal administration of parbendazole (PBZ) on the flow rate of bile and the pharmacokinetic behaviour of oxfendazole (OFZ) was examined in sheep. PBZ given at 18, 9 and 4.5 mg/kg resulted in a dose‐related reduction in bile flow rate which was also inversely related to changing concentration of PBZ and its metabolites in plasma.Co‐administration of 4.5 mg PBZ/kg with 5.0 mg [14C]‐OFZ/kg resulted in increased concentrations of fenbendazole (FBZ), OFZ and fenbendazole sulphone (FBZ‐SO2) in plasma, although total14C levels remained unchanged compared with that observed when OFZ alone was administered. The presence of PBZ also reduced biliary secretion of14C by 22% and ‐altered the relative proportions of OFZ metabolites in bile during the 72‐h experimental period. The ratio of 4′‐hydroxy‐OFZ (OH‐OFZ) to 4′‐hydroxy‐FBZ (OH‐FBZ) changed from 7:1 in the absence of PBZ to approximately 1:1 in the presence of PBZ. There was no change in urinary or faecal14C excretion. The PBZ‐induced effects were temporary since the pharmacokinetic behaviour of OFZ given alone two weeks before was similar to that given two weeks after PBZ co‐administration.It is suggested that the presence of PBZ temporarily slowed hepatic metabolism and biliary secretion of OFZ metabolites butconcomitantly increased extra‐biliary transfer of OFZ andor its metabolites from plasma into the gastrointestinal tract. Elevated exposure of parasites in the gut wall to plasmaderived drug, coupled with higher concentrations of anthelmintically active OH‐FBZ secreted in bile, could contribute to the previously reported increased efficacy o

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00981.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of a parenteral formulation of metoclopramide (mono‐chloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5‐mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min postdosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two‐compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half‐life of 0.62 h and a volume of distribution of the central compartment of 1.34 I/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post‐dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two‐compartment open model with first‐order absorption. The mean biological half‐life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5‐mgfkg dose administere

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00982.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non‐lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 ± 1.145 (mean ± SD) I/kg, mean elimination half‐life was 82 min, and clearance was 34.6 ± 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmaco‐kinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00983.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In sheep, beta‐endorphin (1 and 2 μg/kg) administered into the third cerebral ventricle caused a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of infusion, and the average amplitude of primary rumen contractions, were inhibited. Beta‐endorphin caused general psychomotor excitability. These results suggest that an inhibitory p and 6 opioid system is involved in the control of forestomach motility and general behaviour in sheep. All effects of beta‐endorphin were completely prevented by i.c.v. 6‐hydroxydopamine (6‐OHDA, 18.2 μg/kg) pre‐treatment. These results suggest that beta‐endorphin‐induced inhibition of rumen motility is due to central noradrenergic system activation. The exact location of this noradrenergic system remains

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00984.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The prescribing of drugs for case in veterinary medicine in Norway was investigated through a cross‐sectional survey. Of the 8741 prescriptions issued for animals included in this study 22% were for drug use in veterinarians' practices. Drugs from all but one therapeutic group were prescribed for use in animals. On average, 49% of the prescriptions were for vererinairy prepirations, 43% were for human preparations, and 8% were for formulations prepared by pharmacies. Of prescriptions for specific animal species, 27% of the preparations were not approved for the intended animal species. The corresponding figures for prescriptions of veterinary and human preparations were 7% and 41%, respectively. Of prescriptions for production animals 17% of the preparations were not approved for the intended animal species, and for pets this figure was 30

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00985.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of niastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiraniycin at a dose of 30 000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significanlly longer (P<0.01) in the milk (20.7 ± 2.7 h) than in plasma (4.0 ± 1.6 h). An average milk‐to‐plasma ratio of 36.5 ± 15 was calculated from the area concentration‐time curves. Severid pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction absorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for niaximal concentration in the milk. However, the two routes were bio‐equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland. These data indicate that spiramycin concentrations in milk were much higher than in plasma and were dependent on the route of administration. The two routes were bioequivalent for the length of time the milk concentrations exceeded theMIC, which is important for establishing dosage

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00986.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics of intravenously and orally administered enrofloxacin was determined in fingerling rainbow trout (Oncorhymhur mykiss). Doses of 5 or 10 mg enrofloxacin /kg body weight were administered intravenously to 26 fish for each dose and blood was sampled over a 60‐h period at 15°C. Two groups of fish were treated orally with 5, 10, or 50 mg/kg (80 fish/dose at each temperature) and held at 15°C or 10°C during the 60‐h sampling period. Following intravenous administration, the serum concentration—time data of enrofloxacin in rainbow trout were best described by a two‐compartment open model for both doses of 5 and 10 mg enrofloxacin/kg. The hybrid rate constants a and β did not differ between doses. The distributional phase was rapid with a half‐life of 6–7 min for both doses. Overall half‐lives of elimination were 24.4 h (95% CI = 20.2–30.8) and 30.4 h (24.241.0), respectively, for the 5– and 10‐mg/ kg doses. A large Vd(area)was observed following dosing of either 5 or 10 mg enrofloxacin/kg,: 3.22 and 2.56 l/kg, respectively. Whole body clearance for 5 mg/kg was 92 ml/h.kg and 58 ml/h‐kg at the 10‐mg/kg dose. Following oral administration, the serum concentration—time data for enrofloxacin were best described as a one‐compartment open model with first‐order absorption and elimination. ApparentKaover all doses at 10°C averaged 62% less than apparentKa, at 15°C. Estimates of the apparentt(1/2)eover both temperatures ranged from 29.5 h (18.4–73.4) to 56.3 h (38.3–106.6). Bioavailability averaged 42% over all doses at 15°C and was decreased to an average of 25% at 10°C. Peak serum concentrations appeared between 6 and 8 h following dosing. A dose of 5 mg/kg/ day was estimated to provide average steady‐state serum concentrations at 10°C that are approximately 4.5 times the highest reportedMICvalues forStreptococcusspp., the fish pathogen least sensitive to enrofloxacin. Owing to the long apparent half‐life of elimination of enrofloxacin in fingerling trout, it would take approximately 5 to 9 days to achieve these predicted steady‐state serum concentrations; this estimate is important when consid

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00987.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetic behavior of sodium amoxicillin was studied after intravenous administration to six sheep and five goats to determine if there are species differences in disposition. The plasma drug concentrations vs. time following intravenous administration of 10 mg/kg were best described by the biexponential equationsCp= 42.9e‐0.077.t+ 3.68e‐0.0134‐tfor goats, andCp= 53.5e‐0.06‐t+ 1.69e‐0.015‐tfor sheep. The terminal disposition half‐lives for sheep and goats were 46.3 and 66.9 min respectively and were not significantly different. Amoxicillin clearance for sheep and goats were 10.1 and 11.4 ml/min.kg respectively. There were no significant differences between any of the pharmacokinetic parameters measured in

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00988.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The dopamine antagonist metoclopramide monohydrochloride (MC) and the serotonin agonist quipazine maleate (Q were administered to steers by both the oral and intravenous (i.v.) routes. Dose‐response studies were designed to determine the effects of these drugs on serum prolactin (PRL) concentrations. Parameters subjected to analysis included maximal serum PRL concentrations within 1 h and the areas under the PRL response curves over time. At 1,4, and 8 mg/kg i.v., and at 15, 30, 45, and 60 mg/kg orally, MC increased (P<0.05) serum PRL concentrations (difference between maximal and basal serum PRL concentrations) and increased (P<0.05) areas under the PRL response curves except for 1.0 mg/kg i.v. Doses of MC greater than 60 mg/kg and Q at all dosage rates were considered toxic. These studies determined a dose‐response to MC in terms of serum PRL concentration and indicate that MC is well tolerated and effective for elevating serum PRL concentrations in steers. Furthermore, 4 mg/kg i.v. and 15 mg/kg orally could be considered the preferred dosage rates due to a plateau in the response above those ra

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1992.tb00989.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY