bluuebunny/crossref_metadata_2025 huggingface dataset:
Trimetaquinol relaxes bovine pulmonary arteries in vitro through a non‐beta‐adrenergic mechanism
Authors: MIRBAHAR K. B. , EYRE P.
Published: April 2008

Trimetaquinol (TMQ), a synthetic β‐adrenoceptor stimulant (Iwasawa & Kiyomoto, 1967) has been shown to relax airway smooth muscle of guinea‐pig, cat and horse (Iwasawa & Kiyyomoto, 1967; Brittain, Jack & Ritchie, 1970): pulmonary vein of calf and horse (Hanna, Hambleton & Eyre, 1980;Hanna& Eyre, 1979) and also to benefit patients with mild to moderate asthmatic symptoms (Yamamura & Kishimoto, 1968). However, evidence has been provided which suggests that TMQ has a nonselective β‐adrenergic action and has some papaverine‐like characteristics (Brittain et al., 1970; Newman, Colella, Spainhour, Brann, Zapko‐Potapovich & Wardell, 1978). More recently, Hanna et al., 1980, using bovine pulmonary vein, reported that the venodilator effect of TMQ was neither inhibited by propranolol nor potentiated by phentolamine. These authors further emphasized the structural similarity between TMQ and papaverine. This consideration, coupled with the possibility that inhaled bronchodilators as well as endogenous sympathomimetics may alter pulmonary vascular tone and consequently pulmonary blood flow, the present investigation was undertaken to study the effects of TMQ on bovine pulmonary arteries.
The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and ADH on electrolyte excretion in ponies
Authors: ALEXANDER F.
Published: April 2008

The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and antidiuretic hormone (ADH) on the urinary and faecal excretion of water and electrolytes by ponies was studied. Ethacrynic acid, bumetanide, and frusemide given intravenously, increased urinary sodium excretion, and, excepting frusemide, decreased faecal sodium excretion. Given by stomach tube ethacrynic acid reduced urinary and faecal sodium. Bumetanide, given intravenously, spironolactone, frusemide and ADH increased urinary sodium and all except frusemide intravenously decreased faecal sodium regardless of route of administration. Ethacrynic acid and bumetanide, given by stomach tube or intravenously decreased urinary and faecal potassium excretion, as did spironolactone and frusemide given orally. Ethacrynic acid and bumetanide given orally or intravenously, frusemide given orally and ADH intranasally reduced urinary chloride excretion; these same drugs by the same routes also reduced faecal chloride excretion. Excepting frusemide given intravenously, and ethacrynic acid orally, the effect of the drugs studied was not the same on urinary sodium excretion as on faecal sodium excretion. This suggested that different mechanisms were involved in the control of sodium excretion by the kidney and in the gut. There were similarities in the treatment of potassium and chloride by these organs.
Modification by domperidone of dopamine‐ and apomorphine ‐ induced inhibition of extrinsic ruminal contractions in goats
Authors: MAAS C. L. , van DUIN C. Th. M. , van MIERT A. S. J. P. A. M.
Published: April 2008

Goat ruminal strips reacted with an increase in smooth muscle tone after exposure to apomorphine. This rise in tone could be blocked by domperidone, but not by naltrexone. In vivo, both dopamine and apomorphine caused inhibition of extrinsic ruminal contractions. These effects were completely prevented by domperidone pretreatment, whereas naltrexone was not an effective antagonist. These results suggest that apomorphine‐induced inhibition of rumen motility is due to DA‐receptor activation. The exact location of these DA‐receptors remains to be determined.
Distribution of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol in serum and subcutaneous chamber fluid
Authors: ZIV G. , WANNER M. , NICOLET J.
Published: April 2008

Penetration of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol into interstitial fluid of calves was estimated using subcutaneously implanted, multiple perforated spherical polypropylene capsules as a model. Antibiotic concentrations were determined in simultaneously withdrawn serum and capsular fluid (CF) samples at intervals after single and multiple intramuscular injections of antibiotics at recommended dose schedules. Peak concentrations of penicillin G in CF were 57% of those in serum, and the drug was eliminated from CF at a slower rate than from serum. Dihydrostreptomycin diffused into CF to a limited degree and was eliminated from CF much more slowly than from serum leading to gradual drug accumulation in CF upon repeated dosing. Multiple injections of oxytetracycline resulted in CF drug levels comparable with those in serum. Concentrations of chloramphenicol in CF were generally similar to free (non‐protein bound) serum drug levels. CF concentrations of penicillin G were within the range of the minimal inhibitory concentrations of the drug for pathogenic gram positive micro‐organisms and CF levels of dihydrostreptomycin, oxytetracycline, and chloramphenicol were apparently sufficient to inhibit the majority of gram negative pathogens involved in bovine injections. Advantages and limitations of the tissue cage model are briefly discussed.
Gentamicin sulfate in the horse: serum, synovial, peritoneal, and urine concentrations after single dose intramuscular administration
Authors: BROWN M. P. , STOVER SUSAN M. , KELLY R. H. , FARVER T. B.
Published: April 2008

Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48‐h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 μg/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 μg/ml and 3.92 μg/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and were not measurable at 48 h. Urine gentamicin concentration was relatively high, with a mean peak concentration of 424.9 μg/ml at 1 h after drug administration.
25‐OH‐D3 Concentrations in serum from healthy and paretic post parturient cows
Authors: KÄÄNTEE ESA , KURKELA PAAVO
Published: April 2008

The serum 25‐OH‐D3, Ca, P, and Mg concentrations in thirty‐seven cows that had calved in March April were studied in this trial. Twenty‐three had puerperal paresis. Values observed in this group were Ca, 1.27 ± 0.3 mmol/l, P, 1.63 ± 0.82 mmol/l, Mg, 1.14 ± 0.27 mmol/l, and 25‐OH‐D3, 32.7 ± 22 μg/l. In the fourteen age‐matched healthy control cows from the same herd values were Ca, 1.93 ± 0.5 mmol/l, P, 3.09 ± 1.28 mmol/l, Mg, 1.01 ± 0.3 mmol/l and 25‐OH‐D3, 31.5 ± 19.7 μg/l. The range of values for the cows serum 25‐OH‐D3 concentration was l't; 3.2 to 76 μg/l. No differences could be established in terms of 25‐OH‐D3 concentrations between the groups.
Disposition of gentamicin in the genital tract of cows*
Authors: AL‐GUEDAWY SAYED A. , NEFF‐DAVIS CAROL A. , DAVIS LLOYD E. , WHITMORE HOWARD L. , GUSTAFSSON BORJE K.
Published: April 2008

The distribution of gentamicin (G) in plasma and uterine lumen was studied following intramuscular (i.m.) and intrauterine (i.u.) treatment. A Foley catheter was inserted into one uterine horn and retained in place by inflation of the cuff. This provided a closed system for collection of uterine lumen samples and analysis of the concentration of gentamicin for 6 h following treatment.

Four normal cycling and healthy cows in dioestrus were given i.m. injections of 4 mg gentamicin/kg BW and another two were given i.m. injections of 2 mg gentamicin/kg BW gentamicin. The uteri were infused with 50 ml saline containing phenolsulphonphthalein (PSP) indicator.

Blood and infused solution (IS) samples were periodically collected during the 6‐h period following i.m. administration. Six hours after injection, approximately 183.7 μg gentamicin and 39.4 μg gentamicin were accumulated in the uterine lumen of cows receiving 4 mg gentamicin/kg BW and 2 mg gentamicin/kg BW, respectively. The amount of gentamicin reaching the blood stream after i.m. administration of 4 mg gentamicin/kg BW was 2.89 times that reached after administration of 2 mg gentamicin/kg BW based on the area under the curve of plots of plasma concentration of gentamicin versus time.

Four normal‐cycling and healthy cows in dioestrus were given i.u. infusions of gentamicin (225–275 mg) diluted in 50 ml saline containing PSP indicator using a Foley catheter in a closed system. Samples from the IS and blood were collected at various intervals for 6 h after infusion. Following i.u. infusion of gentamicin, an average of 29.4% of the dose was absorbed into the bloodstream. The majority of the dose of gentamicin (70.6%) remained in the uterine lumen throughout the 6‐h period.
Determination of lidocaine concentrations producing therapeutic and toxic effects in dogs
Authors: WILCKE J. R. , DAVIS L. E. , NEFF‐DAVIS C. A.
Published: April 2008

Lidocaine was infused at a fixed zero‐order rate to eight healthy mongrel dogs until tonic extension (n= 5) and cortical seizures (n= 7) were produced. Lidocaine concentrations determined at 5‐min intervals were used to calculate concentrations at which these effects occurred. The tonic extension phase occurred at a mean lidocaine concentration of 8.21 ± 1.69 μg/ml. After a 1‐month rest period, the same dogs were anaesthetized and ventricular tachycardia was produced by administering ouabain. Lidocaine was again infused at a fixed zero‐order rate until all beats of ventricular origin were abolished. This occurred at a mean lidocaine concentration of 6.25 ± 1.49 μg/ml.
The recombinant DNA technology
Authors: TIEMEIER DAVID C.
Published: April 2008

The recombinant DNA technology or DNA cloning permits the isolation, amplification, and precise manipulation of specific DNA fragments. This is generally accomplished by linking or recombining the desired DNA fragment with a DNA molecule, termed the vector, which is capable of directing the replication of itself in a suitable host cell and any DNA segment covalently attached to it. Using this and associated technologies, it is possible to produce large amounts of specific proteins and to modify cell types by introducing the genes for proteins that are otherwise absent. Moreover, it is now possible to construct variants of naturally‐occurring proteins with improved biological or physical properties.
Age‐dependent pharmacokinetics of oxytetracycline in ruminants
Authors: NOUWS J. F. M. , VAN GINNEKEN C. A. M. , ZIV G.
Published: April 2008

Oxytetracycline (OTC) was administered intravenously (i.v.) to 3‐and 12‐week‐old calves and lactating cows, and both i.v. and intramuscularly (i.m) to 14‐week‐old calves and non‐lactating cows. Concentrations of OTC were determined in plasma and were analysed kinetically. The pharmacokinetic parameters which were derived using the three‐compartment open model were inadequate to describe plasma drug levels in six out of the 23 animals treated i.v., and, therefore, model‐independent kinetic parameters were utilized for evaluating age‐dependent pharmacokinetics of OTC. In the 3‐week‐old calves, the total body clearance (Clb) was 0.0022 ml/min/kg, the total distribution volume (Vd area) was 2.48 l/kg, and the distribution volume of the central compartment (V1) was 0.56 l/kg. Mean values for Clb, Vd area, and V1 in 3‐week‐old calves were two‐, three‐ and four‐fold greater, respectively, than the corresponding values in cows. Mean values of Clb and Vd area for the 12‐and 14‐week‐old calves were intermediate between the corresponding values in 3‐week‐old calves and cows. Dose and state of lactation did not affect the model‐independent parameters. The i.v. and i.m. data illustrated that the recommended dose levels of OTC in young calves should be twice those employed in cows for obtaining similar plasma OTC concentration‐time profiles.
Preparation and properties of monoclonal antibodies to the anabolic agent zeranol
Authors: CARTER A. P. , DIXON S. N. , BEW M. H.
Published: April 2008

Monoclonal antibodies have been produced using two haptens, zeranol‐7‐hemisuccinate coupled to bovine serum albumin and zeranol‐16‐carboxypropyl ether coupled to human serum albumin. An assessment of cross‐reactivity demonstrated that the monoclonal antibody raised against the 7‐hemisuccinate derivative reacted with zeranol (100%), talernol (12%), zearalenone (17%), zearalanone (100%) and α‐and ß‐zearalenol (17% and <0.01%, respectively). In contrast the antibodies to the 16‐carboxypropyl ether derivative reacted only with zeranol (100%) and also with a α‐zearalenol (13‐16%). All monoclonal antibodies were more specific than the polyclonal antibodies raised to the same haptens by conventional methods using sheep.
Evaluation of a sponge‐on therapy for canine scabies
Authors: FOLZ S. D. , KRATZER D. D. , KAKUK T. J. , RECTOR D. L.
Published: April 2008

Forty dogs (20 treated, 20 controls) were utilized to evaluate a new treatment for naturally acquired canine scabies. A liquid concentrate formulation of amitraz was diluted and applied as a sponge‐on therapy. Ninety‐four percent of the dogs treated with the scabicide were cleared of mites and returned to clinical normality with a single topical treatment; one dog was retreated, cleared of mites and was also returned to normality. All dogs treated with the miticide responded clinically, therefore the treatment also may be useful when trial therapy is necessary to differentially diagnose the disease. The miticide was well tolerated by all dogs, and there was no evidence of dermal or ocular irritation. Topical treatment with the liquid concentrate was efficacious and safe as a therapy for naturally acquired canine scabies. Placebo controls did not improve clinically and these animals retained their mite populations.
Clinical pharmacokinetics of carbenicillin, carfecillin, ticarcillin and BL‐P 1654 in dairy cows
Authors: NOUWS J. F. M. , ZIV G. , van GINNEKEN C. A. M. , VREE T. B.
Published: April 2008

The minimal inhibitory concentrations (MIC) of carbenicillin, ticarcillin and BL‐P 1654 for gram‐negative udder pathogens were determined using the agar plate dilution method. The MIC of the drugs for 50% and 90% of the isolates examined ranged for Escherichia coli and Aerobacter spp. from 1.56 to 25 μg/ml, and for Klebsiella spp. and Pseudomonas spp. from 3.12 to 50 μg/ml. The Serratia spp. were relatively non‐susceptible for the drugs studied (MIC greater than 50μg/ml).

Each drug was administered intravenously at 5 g and 15 g per cow to different groups of cows with normal and inflamed quarters of the udder. Distribution and elimination kinetic parameters calculated from serum drug level data were very similar to those of other beta‐lactam antibiotics. Although drug concentrations in milk from inflamed quarters were higher than in milk from normal quarters, they were considerably below the MIC for the majority of gram‐negative udder pathogens. The data suggest that parenteral treatment of gram‐negative udder infections with carbenicillin, carfecillin, ticarcillin and BL‐P 1654 at the dose levels used in the present study is unlikely to result in a bacteriological cure and would probably be clinically ineffective.
Clearance of penicillin G in the newborn calf
Authors: SHORT CHARLES R. , WHITE MARY B. , VARMA KANWAL J. , POWERS THOMAS E. , POWERS JEAN D.
Published: April 2008

Sodium penicillin G was administered intravenously (4545 IU/kg) to calves on the day of birth (12‐24 h old) and at 5, 10, and 15 days of age. Serum was collected at varying intervals for 120 min after injection and analysed for penicillin G. The mean total body clearance (ClB) of penicillin G on the day of birth was 2.98 ml/min/kg compared to 4.83 ml/min/kg at 5 days, 3.11 ml/min/kg at 10 days and 4.65 ml/min/kg at 15 days of age. Clearances at 5 and 15 days were significantly (P<0.05) higher than on the day of birth. The half‐life (t1/2ß), however, did not change significantly over the 15‐day period of the study. These results indicate that the newborn calf has an appreciable ability to excrete penicillin G before it is 24 h old, and that total body clearance of the antibiotic increases rapidly in the immediate postnatal period.
Permeability of the blood‐milk barrier to methylene blue in cows and goats
Authors: ZIV G. , HEAVNER J. E.
Published: April 2008

A 2% aqueous solution of methylene blue was administered as a single intravenous (i.v.) bolus injection (10 mg/kg) to six lactating cows and seven lactating goats and as a continuous i.v. drip to five lactating goats. The same dose was administered as a 10% solution by intramammary infusion to five lactating goats. Blood and milk samples collected at various times after these treatments were assayed for the drug by a colorimetric method. Methylene blue, a highly charged molecule (pKa<1), passed readily from blood into milk; drug concentrations in milk 4‐36 h after the single i.v. bolus injection were higher than those in blood. When examined at constant methylene blue levels in blood, a milk‐blood ratio of 5: 1 was observed. After intramammary infusion, the drug passed quickly into systemic circulation, peaked at 3 h and was still detectable in blood 12 h after infusion. The drug appeared in the urine within 15 min after intramammary infusion. The rapid movement of the drug across the blood‐milk barrier cannot be explained on the basis of its known physicochemical properties or according to the pH‐pKa passive diffusion concept.
Plasma concentration, mammary excretion and side‐effects of phenylbutazone after repeated oral administration in healthy cows
Authors: MARTIN K. , ANDERSSON L. , STRIDSBERG M. , WIESE B. , APPELGREN L.‐E.
Published: April 2008

Seven clinically healthy dairy cows were each given 2.5 gphenylbutazone (approximately 5 mg/kg body weight) by oral administration twice daily for 8 days. The concentrations of phenylbutazone in plasma and milk and several blood parameters were studied. The minium plasma concentration during steady state was 100.4 ± 7.3 μg/ml. During the same period the milk concentration never exceeded 1% of the plasma concentration. The elimination half‐life in plasma was 38.6 ± 3.7 h. Five days after administration had been discontinued, the milk concentration was 0.05 ± 0.01 μg/ml. All seven cows were clinically healthy throughout the experiment. The most pronounced side‐effect of the blood parameters studied was a decreased concentration of leucocytes to about two‐thirds of the control value. This might have a pronounced influence on the effectiveness of the immune system. There was also a significant decrease in total bilirubin indicating a decrease in the breakdown of erythrocytes.
A correlation of toxicity of albendazole and oxfendazole with their free metabolites and bound residues
Authors: DELATOUR P. , GARNIER F. , BENOIT E. , LONGIN CH.
Published: April 2008

The possible correlations between embryotoxicity, plasma kinetics of toxic metabolites and covalent binding of metabolites to foetal tissues were studied using two drugs, albendazole and oxfendazole. In the rat, the metabolic inhibitor, SKF‐525A, induced changes in embryotoxicity which were well correlated with plasma levels of identified embryotoxic metabolites, but not with the levels of foetal tissue bound drug metabolites.
Effects of disopyramide on the electrocardiogram and ventricular function in the unanesthetized dog*
Authors: CROSBY H. H. , HAMLIN R. L. , STRAUCH S. M.
Published: April 2008

The antiarrhythmic compound disopyramide has been shown to possess negative inotropic effects. The present study was conducted to establish the effects of graded doses of disopyramide on ventricular function and electrocardiograms from healthy, awake dogs. Electrocardiograms and echocardiograms were obtained during a control period, and during an experimental period in which the six dogs on test received 7.5, 15 or 30 mg disopyramide per kg body weight orally three times per day. Six other dogs served as vehicle controls. No changes of statistical significance occurred in heart rate. The PQ interval was prolonged at all doses, the QRS complex was prolonged only at the highest dose, and the QT interval was prolonged at the intermediate and high doses. Left ventricular pre‐ejection period (PEP) was prolonged in a dose‐dependent relationship, and the left ventricular ejection time (ET) was shortened only at the highest dose. The percent shortening fraction of the left ventricle (%ΔD) decreased significantly at intermediate and high doses, while the ratio of pre‐ejection period to ejection time increased in a dose‐dependent relationship. Conclusions are that even in therapeutic levels disopyramide produces significant reduction in left ventricular function, and that ratio of PEP/ET correlates better with the dose of disopyramide than did %ΔD. This study demonstrates the feasibility of evaluating cardiac effects of compounds by non‐invasive means.
Methylene blue: effects and disposition in sheep
Authors: BURROWS GEORGE E.
Published: April 2008

The disposition and urinary excretion pharmacokinetics of methylene blue were determined after its intravenous administration at 15 mg/kg to mature female sheep. Comparisons were made between methylene blue administered alone or subsequent to 50 mg/kg sodium nitrite. The overall elimination rate constant (ß) of methylene blue, 0.0076 ± 0.0016 min‐1, was not influenced by prior administration of sodium nitrite. However, the distribution rate was significantly altered by sodium nitrite. Very little of the methylene blue was eliminated in the urine either intact or as leucomethylene blue in spite of its relatively short half life. Toxicologic assessment was carried out using LD50 determination, methemoglobin production and hematologic effects as evaluation parameters. Methemoglobin production was minimal with doses as high as 50 mg/kg and no significant hematologic changes were seen up to 4 weeks after a total dose of 30 mg/kg methylene blue. The 24 h LD50 for intravenous methylene blue administered as a 3% solution was 42.3 mg/kg with 95% confidence interval limits of 37.3 to 47.9 mg/kg. From these data it appears that as conditions may warrant, the dosage of methylene blue may be safely increased up to at least 15 mg/kg in therapy of severe methemoglobinemias.
Pharmacokinetics of cefotaxime and probenecid in sheep with normal and reduced renal function
Authors: GUERRINI V. H. , FILIPPICH L.J. , ENGLISH P. B. , CAO G. R. , BOURNE D. W. A.
Published: April 2008

The pharmacokinetics of cefotaxime and probenecid, given by intravenous injection, were determined in six Merino ewes which had been subjected to a 75% reduction in renal mass. These results were compared with results previously determined in sheep with normal renal function. In the sheep with reduced renal mass, the following significant changes in parameter values for cefotaxime were observed. The elimination rate constant (kel) decreased by 47%, the apparent volume of the central compartment (Vc) decreased by 59%, the steady state volume (Vss) decreased by 50%, and the total body clearance (ClB) decreased by 78%. The rate constant for distribution of drug into tissues (k12) increased 6.9 times, the rate constant for distribution out of tissues (k21) increased 3.7 times, and the area under the plasma concentration‐time curve (AUC) increased by a factor of 4.9.

The parameter values, determined in sheep with reduced renal mass, for probenecid plasma half‐life, Vss and the rate constants k12, k21 and kel were not significantly different from the values obtained previously in sheep with normal renal mass. However, the rate constant for renal excretion of probenecid (kc), renal clearance (ClR), ClB and Vc decreased by 79, 90, 54 and 36%, respectively.

The results indicate that reduced renal mass increased the plasma half‐life for cefotaxime as well as increasing its diffusion into tissue. In the case of probenecid the overall distribution and elimination kinetics were not altered by reduced renal mass; however, the rate of urinary excretion of the drug was reduced.
Monitoring for antibiotic resistance in enterococci consequent upon feeding growth promoters active against Gram‐positive bacteria
Authors: LINTON A. H. , HINTON M. H. , AL‐CHALABY Z. A. M.
Published: April 2008

Linton, A.H., Hinton, M.H. & Al‐Challaby, Z.A.M. Monitoring for antibiotic resistance in enterococci consequent upon feeding growth promoters active against Gram‐positive bacteria. J. vet. Pharmacol. Therap. 8, 62–70.

Commercial chicken and pig farms, using different growth promoters, were monitored for enterococci resistant to a range of antibacterial agents. Due to inconsistent findings attributed to uncontrollable factors, chickens kept under experimental conditions were also studied. A total of 4216 isolates from all the surveys were examined. Resistant isolates were often encountered, even in control groups, suggesting complex population changes not necessarily solely connected with the influence of the growth promoters. It was concluded that comprehensive methods for differentiating strains are necessary to unravel this problem.

A. H. Linton, Department of Microbiology, University of Bristol, Bristol, Avon BS8 ITD, England.
The effect of copper on intact cattle erythrocytes
Authors: ASANO R. , HOKARI S.
Published: April 2008

Asano, R. & Hokari, S. The effect of copper on intact cattle erythrocytes. J. vet. Pharmacol. Therap. 8, 157–164.

The effect of copper on intact cattle erythrocytes was investigated in vitro. When treated with copper, a decrease in the GSH content, accumulation of copper in the cell, loss of potassium and gain of sodium, cross‐linking of membrane proteins, and echinocytic transformation were observed. All of these phenomena seem to be caused by a potent oxidant action of copper. These icy totoxic effects of copper were markedly inhibited by the addition of bovine serum albumin in the incubation medium. These results may help to understand the mechanism of hemolysis associated with copper poisoning in vivo.

Ryuji Asano, Department of Veterinary Pharmacology, College of Agriculture and Veterinary Medicine, Nihon University, Kameino, Fujisawa, Kanagawa 252, Japan.
Pharmacokinetics of anti‐epileptic drugs in the dog: a review
Authors: FREY H.‐H. , LÖSCHER W.
Published: April 2008

Frey, H.‐H. & Löscher, W. Pharmacokinetics of anti‐epileptic drugs in the dog: a review. J. vet. Pharmacol. Therap. 8, 219–233.

Dr H.‐H. Frey, Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstrasse 20, D‐IOOO Berlin 33, West Germany.
Gallbladder motility in sheep: effects of cholecystokinin and related peptides
Authors: RUCKEBUSCH Y. , SOLDANI G.
Published: April 2008

Ruckebusch, Y. & Soldani, G. Gallbladder motility in sheep: effects of cholecystokinin and related peptides. J. vet. Pharmacol. Therup. 8, 263–269.

Gallbladder motility was recorded as tonic and small amplitude (rhythmic) contractions in conscious sheep fitted with miniaturized strain‐gauge force transducers located in the corpus and fundus. Nichrome wire electrodes were chronically implanted in the gastroduodenal area. Both tonic and superimposed rhythmic gallbladder contractions were increased during feeding. They decreased during the periodic phases of antroduodenal quiescence. The excitatory effects on gallbladder and antroduodenal motility were mimicked by pilocarpine and blocked by atropine. Cholecystokinin (CCK‐OP) and caerulein elicited motor responses of the gallbladder in a dose‐related manner without antroduodenal stimulation. In contrast, pentagastrin induced gallbladder motor responses with concomitant stimulation of the antroduodenal area. The results suggest that feeding may act to trigger gallbladder motor activity through a mechanism related to the increased antroduodenal activity. Direct effects of CCK‐OP and caerulein confirm that gallbladder motor function is also mediated through specific receptor sites.

Professor Y. Ruckebusch, Ecole Nalionale Vélérinaire, 23 chemin des Capelles, 31076 Toulouse Cédex, France.
Potentiation of the anthelmintic activity of oxfendazole by parbendazole
Authors: HENNESSY D. R. , LACEY E. , PRICHARD R. K. , STEEL J. W.
Published: April 2008

Hennessy, D.R., Lacey, E., Prichaid, R.K. & Steel, J.W. Potentiation of the anthelmintic activity of oxfendazole by parbendazole. J. vet. Pharmacol. Therap. 8, 270–275.

The ability of parbendazole (PBZ) to potentiate co‐administered oxfendazole (OFZ) was investigated. Administration of a range (1.35–36.0 mg/kg) of doses of PBZ with 4.53 mg OKZ/kg demonstrated that signilicant potentiation occurred at 4.5 mg PBZ/kg. At 4.5 mg PBZ/kg, the area under the plasma OKZ concentration curve was about twice that obtained from oral administration of OFZ alone. When tested against benzimidazole‐resistant Haemonchus contorolus and Trichostrongylus colubriformis, the mixture of 4.5 mg PBZ + 4.53 mg OKZ/kg was significantly more effective than 4.53 mg OFZ/kg alone, and PBZ alone showed no activity against these resistant nematodes. The demonstration of PBZ‐OFZ potentiation has indicated a means of obtaining a more effective use of currently available anthelmintics in the treatment of helminthiasis.

Dr D. R. Hennessy, CSIRO Division of Animal Health, McMaster Laboratory, Private Bag No. 1, PO, Glebe, NSW 2037, Australia.
The effect of niclofolan on desert sheep experimentally infected with immature Fasciola gigantica
Authors: ALI B. H. , HASSAN T. , HAROUN E. M. , SAMRA M.T. ABU
Published: April 2008

Eight desert sheep were each infected orally with 500 metacercariae of Fasciola gigantica and, after 4 weeks, four of the animals were given niclofolan orally at the recommended therapeutic dose rate of 7 mg/kg, the other four remaining as controls. One week later, the animals were slaughtered and the fasciocidal effect of the drug was evaluated on the basis of worm burden, haemogram, some plasma constituents, and gross and histopathological lesions of the liver, as indicators of efficacy. The treatment was found to be ineffective, the degree of infection remaining the same as in the untreated control group. The experiment was repeated using eight infected sheep: four were given the drug orally at a dose rate of 10.5 mg/kg, i.e., 1.5 times the recommended dose; and the same parameters were measured as described above. The drug failed to cure the infected sheep, and caused depression, anorexia and weakness. In a third experiment six sheep were infected as before and three were treated with niclofolan by deep i.m. injection at the recommended therapeutic dose of 2 mg/kg. A week later the animals were killed and examined as before. The drug was effective in treating the infection and produced no untoward effects except for transient signs of pain at the site of injection. It seems possible that the oral dose, unlike the i.m. dose, of niclofolan is not absorbed and/or metabolized sufficiently to prevent elimination of the infection.
Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses
Authors: CHRISTENSEN J. M. , BLYTHE L. L. , CRAIG A. M.
Published: April 2008

Phenylbutazone was administered to six Thoroughbred horses in a cross‐over study in which die horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half‐life of phenylbutazone did not change with cimetidine pretreatment; however, lower plasma concentrations of the metabolite gamma‐hydroxyphenylbutazone were observed with cimetidine pretreatments. Plasma concentrations of the metabolite oxyphenbutazone were unchanged with cimetidine pretreatment compared to control values. Twenty‐four‐hour plasma concentrations of phenylbutazone were not different from control values with cimetidine pretreatment. This study suggests that concurrent treatment with cimetidine and phenylbutazone 24 h before race time does not result in elevations of plasma phenylbutazone concentrations above control values.
The effect of albendazole and triclabendazole on colchicine binding in the liver fluke Fasciola hepatica
Authors: FETTERER R. H.
Published: April 2008

Albendazole (ABZ) and its sulfoxide (SX) and sulfone (SO) metaliolites inhibit the binding of :3H‐colchicine, a ligancl with high affinity for tubulin to homogenate preparations of the liver fluke Fasciola hepatica. The relative potency of these compounds is SX > ABZ > SO. The benzimidazoles (cambendazole, parbendazole, oxibendazole and mebendazole), when tested at a concentration of 10 μM, also inhibited colchicine binding to fluke homogenates. However, a potent new benzimidazole flukacide, triclalbendazole (TCB), was without effect on colchicine binding to F hepatica homogenates. When intact flukes were exposed in vivo to 10‐5′M SX for as little as 5 min the subsequent binding of 3H‐colchicine to fluke homogenates was significantly reduced. However, flukes recovered from sheep either 12 or 24 h after treatment with ABZ did not have a decreased ability to bind colchicine, although the non‐specific binding was higher in flukes from treated sheep, suggesting some interaction of drug with tubulin in vivo. ABZ, SX and SO were effective in preventing embryonation of lluke eggs at doses as low as 0.0 1 μM, but TCB was without effect at concentrations as high as 10 μM. The results suggest that ABZ exerts at least part of its anthelmintic effect by interaction with fluke tubulin.
Sulfatroxazole: pharmacokinetics, metabolism and urinary excretion in goats and pigs
Authors: KINABO L. D. B. , NIELSEN POUL
Published: April 2008

The disposition of sulfatroxazole (STZ) has been studied in goats and pigs after intravenous administration of a single dose. The percentage of protein‐binding decreased with increasing plasma concentration in both species. At 100 μg/ml about 85% was bound to plasma proteins in goats, while the corresponding value was only 55% in pigs. Two metabolites of STZ were isolated from urine and identified as N4‐acetyl‐STZ and 3‐sulfaniIarnido‐4‐methyl‐5‐hydroxy‐methyl‐isoxazole (5′‐OH‐STZ). The goats excreted about 80% of the dose in urine. The majority (64%) was excreted as unchanged STZ, while N4‐acetyl‐STZ and 5′‐OH‐STZ made up 19% and 18%, respectively. The pigs excreted 95% of the dose in urine. Unchanged STZ amounted to 30% and N4‐acetyl‐STZ to 70% of the urinary excretion in pigs, while there were only traces of 5′‐OH‐STZ.
Loperamide: evidence for a centrally mediated opioid effect on rumen motility in conscious goats and sheep
Authors: MAAS C. L. , DUIN C. T. M. VAN , MIERT A. S.J. P. A. M. VAN
Published: April 2008

Loperamide inhibited the frequency and amplitude of cyclical contractions of the rumen in conscious goats (100 μg/kg, i.v. and sheep (250 μg/kg, i.v.). In goats, the inhibitory effect of loperamide could be prevented by pretreatment with the opiate antagonist naltrexone (≥ 12.5 μg/kg, i.v.), but not by pretreatment with the dopaminergic antagonist domperidone (500 μg/kg, i.v.). Intra‐cerebroventricular administration of 1 μg/kg loperamide in goats significantly depressed ruminal contraction frequency, whereas intravenous administration of 10 μg/kg loperamide did not affect cyclical motility. Administered via the carotid artery, loperamide (4 μg/kg) depressed both frequency and amplitude of cyclical contractions of reticulum and rumen, whereas the same dose was ineffective via the coeliac artery. In vitro, loperamide (10 nM‐100 μM) had no influence on spontaneous activity or tone of the reticular longitudinal muscle strips. It is concluded that loperamide inhibits cyclical ruminal contractions through a central opioid pathway.
Penetration of oxytetracycline into tissue‐cages in calves
Authors: BENGTSSON B. , LUTHMAN J. , JACOBSSON S.‐O.
Published: April 2008

Concentrations of oxytetracycline (OTC) in serum and tissue‐cage fluid (TCF) from subcutaneous tissue‐cages were determined after single and repeated intravenous and intramuscular doses of 10 mg/kg to calves. Intravenous administration resulted in higher levels, and greater area under curve (AUC) in TCF, than did intramuscular administration. However, the penetration measured as the ratio of AUC in TCF to AUC in serum was equal, and therefore independent of the route of administration. A linear relationship between AUC in serum and AUC in TCF could be demonstrated. Half‐lives of OTC in serum were 4.9 ± 3.1 h after intravenous, and 6.l ± 2.0 h after intramuscular administration. In TCF the half‐lives were 21.5 ± 4.4 h and 24.5 ± 11.5 h after intravenous and intramuscular administration, respectively. Repeated dosing resulted in accumulation of OTC in TCF. Lesser accumulation in older cages indicated altered characteristics of the cages with the passage of time. In serum, no substantial accumulation was seen after repeated i.v. dosing until the dosing interval was shortened to 6 h.
Pharmacokinetics of lithium in the dog
Authors: ROSENTHAL R. C. , KORITZ G. D. , DAVIS L. E.
Published: April 2008

The pharmacokinetics of lithium were determined in eight adult dogs. The data were fitted to a two‐compartment model. Single intravenous doses of lithium chloride, and single oral doses of lithium carbonate were used. The mean plasma lithium half‐life (l½) following the single intravenous dose was 21.6 h, and the mean apparent specific volume of distribution of the central compartment (V′c) was 0.189 l/kg. Mean bioavailability was 78.8% following oral administration.
Amitraz: a tick and flea repellent and tick detachment drug
Authors: FOLZ S. D. , ASH K. A. , CONDER G. A. , RECTOR D. L.
Published: April 2008

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/?, sanguineus for 2 weeks post‐treatment; the treatment was moderately active (63%) during the third week, and at 4 weeks post‐treatment the drug was inactive. Established R. sanguineus populations were also treated, and the diluted liquid concentrate had 100% tick‐detachment efficacy. Repellent activity (99%) was also detected against D. 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 the placebo.
Distribution of kanamycin in ocular tissues of calves
Authors: GEORGE L. W. , REINA‐GUERRA M. , BAGGOT J. D. , MIHALYI JUDY
Published: April 2008

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 with Moraxella 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 tissues in vitro showed 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 intraocular penetration.
Influence of induced disease states on the disposition kinetics of imidocarb in goats*
Authors: ABDULLAH A. SALAM , BAGGOT J. D.
Published: April 2008

The influence of fever, induced by different agents, on the disposition kinetics of imidocarb was determined in goats. Escherichia coli endotoxin (0.2 μg/kg), Trypanosoma evansi (10 in 1 ml sterile glucose citrate), and Infectious Bovine Rhinotracheitis virus (106,5 TCID50) 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. coli endotoxin and IBR virus caused corresponding decreases in apparent volume of distribution and clearance of imidocarb, while fever induced with T. evansi caused 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 reaction per se but also to the pathophysiology of the disease condition.
Characterization of a Pasteurella multocida (serotype B) bovine pneumonic pasteurellosis model and the effect of antimicrobials during peracute infection
Authors: FURROW R. D. , PARBUONI E. L. , McRAE D. T. , GAINES S. A. , GUARNIERI J. A. , CARNEVALE R. A. , APRIL M.
Published: April 2008

A method to produce bovine pneumonic pasteurellosis for experimental purposes was studied and the clinical response of experimentally infected calves to selected antimicrobials was characterized. Male Holstein calves stressed with multiple hot and cold water applications followed by intratracheal inoculation of broth cultures of Pasteurella multocida serotype B developed acute clinical illness consistent with pneumonia. Infected, untreated calves consistently developed classic pneumonic pasteurellosis, infected calves treated with either oxyletracycline or sulfadimethoxine recovered from acute clinical disease, and the uninfected controls remained healthy. This disease model offers potential for use in pharmacokinetic and target tissue drug concentration studies and for dosage titration of drugs intended for treatment of bacterial pneumonias.
The effect of incorporation of cloxacillin in liposomes on treatment of experimental staphylococcal mastitis in mice
Authors: ANDERSON J. C. , KIRBY C. J.
Published: April 2008

The effect of incorporation of cloxacillin in liposomes on the treatment of staphylococcal mastitis was assessed bacteriologically 18 h after treatment of experimental infections in mice caused by two strains of Staphylococcus aureus. Intramammary treatments were cloxacillin incorporated in liposomes, cloxacillin in combination with liposomes, empty liposomes, cloxacillin in saline and saline alone. In none of the experiments did entrapment of cloxacillin within liposomes enhance its antibacterial effects. Electron microscopic studies demonstrated the presence of liposomes in neutrophils which also contained staphylococci. The results support the hypothesis that intracellular staphylococci are metabolically dormant and therefore not susceptible to the action of inhibitors of cell wall synthesis such as cloxacillin.
Pharmacokinetics and diuretic effect of bumetanide following intravenous and intramuscular administration to horses‡
Authors: DELBEKE F. T. , DEBACKERE M. , DESMET N. , STEVENS M.
Published: April 2008

Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 μg/kg. The elimination half‐life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailability was 70–80%. i.m. administration of bumetanide prolonged its plasma half‐life (11–27 min) and enhanced and prolonged its diuretic effect.
Pharmacokinetics and pharmacodynamics of guanidine hydrochloride in an hereditary myasthenia gravis‐like disorder in dogs
Authors: FLAGSTAD A. , NIELSEN P. , ABORG W. TROJ
Published: April 2008

The pharmacokinetic parameters of guanidine hydrochloride were analysed in dogs with an hereditary neuromuscular transmission disorder by the use of 14C‐guanidine hydrochloride. The content of intravenously administrated 14C‐guanidine hydrochloride in plasma, urine and faeces was determined by liquid scintillation counting. The drug was rapidly distributed in the organism with a plasma half‐life of 7–8 h and most was eliminated in the urine.

The clinical and electrophysiological effects of guanidine hydrochloride on the muscular weakness and fatigue induced by exercise were determined after oral and intravenous administration. Guanidine hydrochloride improved muscle‐function, but had no apparent effect when administered during an attack of weakness. An effective level of guanidine in plasma (2–10 Hg/ml) changed the muscle response evoked by trains of repetitive stimulation. The myasthenic decrement during short stimulation trains was unchanged.