ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00022.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Six penicillin preparations were administered to six dogs of various types, both when the dogs were fasted and when fed a standard meal immediately before dosing. The preparations used were: amoxycillin tablets and drops, ampicillin tablets, penicillin V tablets, phenethicillin tablets and cloxacillin capsules. A Latin square design was employed with ampicillin and the two amoxycillin preparations, while three separate cross‐over studies were done with penicillin V, phenethicillin and cloxacillin. Dose rates used were 50 mg/kg for cloxacillin, and 10 mg/kg for the others. A microbiological method was used to assay penicillin in blood samples taken at intervals after dosing. Values for peak plasma drug concentration (Cmax), the time at which it occurred (Tmax), and area under the curve (AUC) were obtained for each curve of drug concentration plotted against time. In fasted dogs, ampicillin showed poorer systemic availability than did amoxycillin, withCmaxand AUC values of less than half those of amoxycillin. The solid and liquid preparations of amoxycillin had similar bioavailability. Ingesta adversely affected the systemic availability of antibiotic from all preparations tested. With ampicillin and both amoxycillin preparations, there were reducedCmaxand AUC and prolongedTmax, indicating slowed and diminished absorption. Feeding did not alterTmaxwith the other drugs, but reduced theCmaxof penicillin V, phenethicillin and cloxacillin and the AUC of cloxacillin. It is suggested that, if minimal impairment of bioavailability by ingesta is desired, then the penicillins commonly administered by mouth (amoxycillin, ampicillin, pencillin V, phenethicillin, cloxacillin) should be given to dogs that are fastin

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00023.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

A topical formulation of amitraz (Mitaban® Liquid Concentrate, The Upjohn Company, Kalamazoo, Michigan, U.S.A.) was evaluated as a tick repellent and detachment agent, and flea repellent. The diluted liquid concentrate (250 p.p.m. active drug) was topically applied as a single treatment to dogs; the concentration was identical to the rate recommended for treatment of demodicosis and scabies. Brown dog tick(Rhipicephalus sanguineus)and American dog tick(Dermacentor variabilis)populations were eliminated and repelled. Repellent activity (92–95%) was observed against/?,sanguineusfor 2 weeks post‐treatment; the treatment was moderately active (63%) during the third week, and at 4 weeks post‐treatment the drug was inactive. EstablishedR. sanguineuspopulations were also treated, and the diluted liquid concentrate had 100% tick‐detachment efficacy. Repellent activity (99%) was also detected againstD. variabilis;the activity was monitored for only 7 days. The ectoparasiticide had low to moderate flea (Ctenocephalides felis) repellent activity (42%) for 4 days post‐treatment; thereafter the treatment was ineffective. Side‐effects were not observed in any of the dogs treated with amitraz, or

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00024.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Xylazine and clonidine, given intravenously, cause an increase in airway pressure in the anaesthetized, ventilated sheep. This increase was dose dependent and was not mediated by histamine, nor was it blocked by the α1‐adrenoceptor antagonist prazosin. However, the increase was abolished by the α2‐adrenoceptor antagonist, idazoxan. When the α2‐adrenoceptor agonists were administered into the cerebrospinal fluid by injection into the cisterna magna there was no increase in airway pressure, although a similar dose given peripherally still produced an effect. These findings would indicate that the increase in airway pressure seen in these sheep, following administration of xylazine and clonidine, was mediated by peripherally located α2‐ad

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00025.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The effect of intramuscular azaperone on the cardiovascular responses to stimulation of the sympathetic nervous system was examined in thiopentone‐anaesthetized stress‐sensitive pigs. Sympathetic stimulation was achieved with the Valsalva‐like manoeuvre, and the intravenous tyramine, isoprenaline and phenylephrine tests. The responses were monitored as the changes in heart rate and blood pressure. Azaperone exerted an a adrenergic blocking action and possibly a mild p adrenergic blocking effect. It also retarded pre‐adrenoreceptor activation of heart rate. It is suggested that azaperone has peripheral actions which could contribute towards its prophylactic effect in preventing stress‐induced death

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00026.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The minimal inhibitory concentration (MIC) of flumequine for 249Salmonella, 126Escherichia coli, and 22Pasteurella multocidaisolates recovered from clinical cases of neonatal calf diarrhoea, pneumonia and sudden death was ≤ 0.78 μg/ml. The pharmacokinetics of flumequine in calves was investigated after intravenous (i.v.), intramuscular (i.m.) and oral administration. The two‐compartment open model was used for the analysis of serum drug concentrations measured after rapid i.v. (‘bolus’) injection. The distribution half‐life (t½α) was 13 min, elimination half‐life (t½β) was 2.25 h, the apparent area volume of distribution (Vd(area)), and the volume of distribution at steady state (Vd(ss)) were 1.48 and 1.43 1/kg, respectively. Flumequine was quickly and completely absorbed into the systemic circulation after i.m. administration of a soluble drug formulation; a mean peak serum drug concentration (Cmax) of 6.2 (ig/ml was attained 30 min after treatment at 10 mg/kg and was similar to the concentration measured 30 min after an equal dose of the drug was injected i.v. On the other hand, the i.m. bioavailability of two injectable oily suspensions of the drug was 44%; both formulations failed to produce serum drug concentrations of potential clinical significance after administration at 20 mg/kg. The drug was rapidly absorbed after oral administration; the oral bioavailability ranged between 55.7% for the 5 mg/kg dose and 92.5% for the 20 mg/kg dose. Concomitant i.m. or oral administration of probenecid at 40 mg/kg did not change the Cmaxof the flumequine but slightly decreased its elimination rate. Flumequine was 74.5% bound in serum. Kinetic data generated from single dose i.v., i.m. and oral drug adminstration were used to calculate practical dosage recommendations. Calculations showed that the soluble drug formulation should be administered i.m. at 25 mg/kg every 12 h, or alternatively at 50 mg/kg every 24 h. The drug should be administered orally at 30 and 60 mg/kg every 12 and 24 h, respectively. Very large, and in our opinion impractical, doses of flumequine formulated as oily suspension are required to produce serum drug concentrations of potentia

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00027.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The ocular distribution of kanamycin following intramuscular, bulbar subconjunctival injection, or after constant rate intravenous infusion to calves was studied. Steady‐state plasma concentrations of kanamycin were achieved in either normal calves, or in those experimentally infected withMoraxella bovis, and the concentrations of kanamycin in the serum, aqueous humor, vitreous body, tears, and the ocular tissues were measured. Kanamycin was not detected in the retina, lens, vitreous body, or the aqueous humor of any eyes, but the concentration of drug in the tears, conjunctiva, cornea and the orbital lacrimal gland of these calves ranged between 18 and 21% of that in serum. At steady‐state plasma levels, the kanamycin concentrations in tears from eyes with keratoconjunctivitis and from normal eyes were similar. A study using lyophilized, powdered, ocular tissuesin vitroshowed that kanamycin was highly bound to the bovine retina and iris, and could be eluted using 0.2 N NaOH. The binding of kanamycin to other ocular tissues, including cornea, conjunctiva and lens, was significantly less.The concentration of kanamycin in the serum and the tears of calves was also measured after intramuscular or bulbar subconjunctival injection. After intramuscular administration of kanamycin (10 mg/kg of body‐weight), the mean serum concentration was maximal at 1 h (32 μg/ml) and remained ≥ 1.0 μg/ml for 8 h. The mean tear concentration was maximal (3.1 μg/ml) at 30 min, and remained ≥ 1.5 μg/ml for only 2.5 h. Following bulbar subjunctival administration of kanamycin (100 mg, single subconjunctival dose), the mean tear concentration was 1127 μg/ml at 30 min, ≤ 4.1 μg/ml at 4 h, and thereafter was ≤ 1.0 μg/ml. It was concluded that kanamycin has limited distribution to the ocular tissues following parenteral administration. Binding of the drug to the ocular pigments may be responsible for its limited int

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00028.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The influence of fever, induced by different agents, on the disposition kinetics of imidocarb was determined in goats.Escherichia coliendotoxin (0.2 μg/kg),Trypanosoma evansi(10 in 1 ml sterile glucose citrate), and Infectious Bovine Rhinotracheitis virus (106,5TCID50) were the agents administered to induce the febrile state. In control and febrile animals the two‐compartment model was used to describe the disposition kinetics of the drug. Fever caused significant changes to occur in the apparent volume of distribution and the body (systemic) clearance of imidocarb, but the half‐life remained unchanged. The statistical significance of the changes in these pharmacokinetic parameters varied with the etiology of the febrile state.E. coliendotoxin and IBR virus caused corresponding decreases in apparent volume of distribution and clearance of imidocarb, while fever induced withT. evansicaused highly significant increases in both pharmacokinetic parameters. It was concluded that the alterations in the disposition kinetics of imidocarb that occurred in the febrile goats were related not only to the febrile reactionper sebut also to the pathophysiology of the disease condi

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00029.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 μg/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15‐sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 ± 0.522 to 4.17 ± 0.679 μg/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 ± 4 to 99 ± 4.9 b.p.m.), and mean arterial pressure significantly increased (83 ± 4.0 to 122 ± 3.4 mm Hg). Heart rate measured immediately prior to epinephrine‐induced arrhythmia formation was significantly increased following xylazine administration (177 ± 8vs78 ± 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed a agonist, potentiated halothane‐induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinep

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00030.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue‐cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmaxof 12.4 μg/ml occurring at a time of 4.6 h and a mean AUQ)_24 of 128 μg‐h/ml. A high mean exudate: plasma AUCo_24 ratio of 0.83 was recorded. Plasma: exudate concentration ratios for phenylbutazone were initially greater than and subsequently less than one; the slower clearance from exudate was indicated by approximatet½βvalues of 4.8 and 24 h for plasma and exudate, respectively. These findings may help to explain the relatively long duration of action of phenylbutazone, in spite of a plasma elimination half‐life of less than 5 h. Lower values of Cmaxand AUC0–24for phenylbutazone passage into peritoneal fluid (6.3 μg/ml and 45 (μh/ml) were recorded, and a limited number of sampling times indicated a similar degree of penetration as into tissue cage fluid. Mean concentrations of oxyphenbutazone in all fluids were lower than phenylbutazone concentrations at all times, but ready penetration of the metabolite into body fluids, especially into inflammatory exudate, occurred suggesting that oxyphenbutazone may contribute to the anti‐inflammatory effect. The hyperaemia of acute inflammation and the high protein levels in inflammatory exudate may both assist passage of phenylbutazone and oxyphenbutazone into exudate. The slower clearance of both compounds from exudate, periton̆ceal fluid and tissue cage fluid than from plasma is similar to previous reports

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1986.tb00031.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY