bluuebunny/crossref_metadata_2025 huggingface dataset:
The biology, pathophysiology and control of eicosanoids in inflammation
Authors: HIGGINS A. J.
Published: April 2008

Higgins, A.J. The biology, pathophysiology and control of eicosanoids in inflammation. J. vet. Pluirmacol. Therap. 8, 1–18.

The involvement in inflammatory conditions of those cyclo‐oxygenase and lipoxygenase derivatives of arachidonic acid (5, 8, 11, 14‐eicosatetraenoic acid), which are known as the eicosanoids, is reviewed iti the light of recent studies. Although it is now generally recognized that cyclo‐oxygenase products are fundamental to the inflammatory process as chemical mediators, and that inhibition of the cyclo‐oxygenase enzyme pathway explains the mode of action of most non‐steroidal anti‐inflammatory drugs (NSAIDs) commonly prescribed in veterinary practice, evidence for the involvement of lipoxygenase products of arachidonate metabolism in inflammation is increasing. The leukotrienes (LTs) are 5‐lipoxygenase‐derived eicosanoids which have been shown to be leucotactic and involved in anaphylactic and hypersensitivity reactions. Leucocytes, drawn to sites of injury by chemotaxis, themselves liberate pro‐inflammatory eicosanoids which perpetuate the response and may aggravate the clinical condition. At therapeutic dose rates, most NSAIDs have no effect on the biosynthesis of LTs, whereas corticosteroids, by inhibiting the release of arachidonic acid, may prevent the formation of both cyclo‐oxygenase and lipoxygenase products. However, because of the undesirable side‐effects of steroids, the clinical use of these agents in treating inflammatory conditions is sometimes limited. Novel non‐steroid inhibitors of cyclo‐oxygenase and lipoxygenase enzyme pathways could offer more effective and safer control of inflammation in animals.

A.J. Higgins, The Royal Veterinaiy College, North Mymms, Hatfield, Hertfordshire AL9 7TA, England.
Pharmacokinetics of ivermectin in sheep following intravenous, intra‐abomasal or intraruminal administration*
Authors: PRICHARD R. K. , STEEL J. W. , LACEY E. , HENNESSY D. R.
Published: April 2008

Prichard, R.K., Steel, J.W., Lacey, E. & Hennessy, D.R. Pharmacokinetics of ivermectin in sheep following intravenous, intra‐abomasal, or intraruminal administration. J. vet. Pharmacol. Therap. 8, 88–94.

The pharmacokinetics of ivermectin in plasma following intravenous, intra‐abomasal, and intraruminal administration to sheep was determined. When given intravenously, ivermectin was very slowly eliminated with a terminal half‐life of 178 h and a volume of distribution at steady state of 5.3 l/kg indicating sequestration in a temporary depot. Intra‐abomasal administration resulted in rapid absorption, a peak plasma concentration of 6O.6 ng/ml at 4.4 h, and 100% bioavailability. However, intraruminal administration produced a much lower peak concentration (17.6 ng/ml at 23.5 h) and bioavailability (25.1%). A subsequent in vitro study indicated that ivermectin may be rapidly metabolized in the rumen.

Dr.J. W. Steel, CSIRO Division of Animal Health, McMaster Lahoratory, Private Bag No. 1, P.O., Glebe, NSW 2037, Australia.
Pharmacokinetics of cefaronide, ceftriaxone and cefoperazone in sheep
Authors: GUERRINI V. H. , FILIPPICH L. J. , CAO G. R. , ENGLISH P. B. , BOURNE D. W. A.
Published: April 2008

Guerrini, V.H., Filippich, L.J., Cao, G.R., English, P.B. & Bourne, D.W.A. Pharmacokinetics of cefaronide, ceftriaxone and cefoperazone in sheep. J. vet. Pharmacol. Therap. 8, 120–127.

The pharmacokinetics of cefaronide (16gm/kg dose), ceftriaxone and cefoperazone (47gm/kg dose), after intravenous (i.v.) administration were determined in six Merino ewes. The mean values for terminal half life, steady state volume of distribution Vd(ss), renal clearance (ClR) and total body clearance (ClB) for cefaronide were 1.5 h, 0.39l/kg, 0.06l/h/kg and 0.16l/h/kg, for ceftriaxone; 1.7 h, 0.30l/kg, 0.08l/h/kg, and 0.22l/h/kg, and 0.7 h, 0.16l/kg, 0.02l/h/kg and 0.16l/h/kg for cefoperazone, respectively. After 5.5 h, approximately 42% cefaronide, and after 8 h, approximately 37% ceftriaxone and 13% cefoperazone, was excreted in urine.

The non‐renal elimination of ceftriaxone and cefoperazone appeared to be more rapid in sheep than is reported in man. Cefaronide was excreted largely unchanged in the urine of sheep. Therefore, the elimination of cefaronide in sheep was similar to that found in man. Cefaronide was well distributed in sheep, whereas ceftriaxone and cefoperazone appeared to be distributed to a lesser degree. These Findings underline the different disposition of drugs in different species.

Dr V. H. Guerrini, Department of Pharmacy, University of Queensland, St Lucia, QLD 4067, Australia.
Effect of lidamidine‐HCl on Escherichia coli heat‐stable enterotoxin‐induced jejunal water and electrolyte secretion in neonatal piglets
Authors: MERRITT A. M. , BERKHOFF H. , HASKELL M. , WILSON J.
Published: April 2008

Merritt, A.M., Berkhoff, H., Haskell, M. & Wilson, J. Effect of lidamidine‐HCl on Escherichia coli heat‐stable enterotoxin‐inducéd jejunal water and electrolyte secretion in neonatal piglets. J. vet. Pharmacol. Therap. 8, 150–156.

Neonatal piglets were anesthetized, and two jejunal loops, 20 cm in length, were prepared. Then, either water or 0.12, 0.25, 0.5 or 1.0mg/kg of lidamidine‐HCl was injected intraduodenally on a randomized basis, one treatment per pig. Following this, a crude heat‐stable enterotoxin (ST) preparation produced from E. coli no. 1261 was injected into the proximal jejunal loop, and trypticase soy broth (TSB) (with osmolality adjusted to equal the enterotoxin preparation) was injected into the distal jejunal loop. Piglets remained anesthetized for 3 h and were then killed. Fluid was collected from the loops for measurement of volume and Na, K and CI concentration. Empty loop lengths were measured.

There was a significant dose‐related reduction of volume and CI content, and a dose‐related, but not significant, reduction in Na content in ST‐treated loops. A comparison of the mean differences in responses between toxin‐and TSB‐treated loops indicated that the major ‘counter‐toxic’ effect of the lidamidine was a dose‐related increase in water and electrolyte absorption.

A. M. Merritt, Department of Medical Sciences, College of Veterinaiy Medicine, University of Florida, Box J‐126, Gainesville, FL 32610, U.S.A.
The effect of prostaglandin E1 on motility of the equine gut
Authors: HUNT J. M. , GERRING E. L.
Published: April 2008

Hunt, J.M. & Gerring, E.L. The effect of prostaglandin E1 on motility of the equine gut. J. vet. Pharmacol. Therap. 8, 165–173.

Prostaglandin E1 was infused intravenously (25, 50 and 75ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain‐gauge force transducers and electrodes. Dose‐dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the proximal jejunum than in the ileum. There was an association between these changes in gastrointestinal activity and the presence of discomfort and diminished gut sounds.

Judith M. Hunt, Department of Veterinary Surgery and Obstetrics, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, U.K.
An improved radioimmunoassay for the anabolic agent hexoestrol, using a monoclonal antibody
Authors: CARTER A. P. D. , COTTINGHAM J. D. , DIXON S. N. , HEITZMAN R.J.
Published: April 2008

A monoclonal antibody was raised against hexoestrol coupled to bovine serum albumin. The antibody cross‐reacted with the stilbenes, diethylstilboestrol (10%) and dienoestrol (4%), but had no cross‐reaction (<0.01%) with other anabolic agents.

A radioimmunoassay method using the monoclonal antibody has been validated and used to measure residues of hexoestrol in the urine of treated cattle. The limit of detection was 0.6 pg/ml urine at the 95% confidence limit. The results were compared with those obtained using polyclonal antibodies. Although there was a good correlation between the results, the use of monoclonal antibody gave more reliable results than those obtained with available polyclonal antibodies. The monoclonal antibody, because of its quality and theoretically limidess supply, is very suitable for use in large scale screening or monitoring programmes for regulating the use of hexoestrol.
Reaction cements as materials for the sustained release of trace elements into the digestive tract of cattle and sheep. II. Release of cobalt and selenium
Authors: MANSTON R. , GLEED P. T.
Published: April 2008

Acid‐base reaction cements, containing salts of copper, cobalt and selenium, were placed in the reticulum of sheep and cattle, and the rate of release of cobalt and selenium from them was measured. The rate of release of cobalt decreased with time but was sufficient to provide adequate supplementation for at least 6 months. After an initial rate of release of 4 mg Se/day for 1‐2 weeks, the mean subsequent rate of release of selenium over a period of 4 months was 0.1 mg Se/day (= 5 μg Se/day/cm2 surface area). Field trials in lambs and growing steers showed that the cement increased the selenium concentration of their blood throughout a summer grazing period.
The nephrotoxic potential of gentamicin in the cat: enzymuria and alterations in urine concentrating capability
Authors: HARDY M. L. , HSU RUEI‐CHING , SHORT C. R.
Published: April 2008

This study investigated the potential for nephrotoxicity of gentamicin in cats by measuring marker enzyme concentrations, [Na], [K], osmolality, and pH of the urine, and blood urea nitrogen (BUN) levels. Gentamicin was administered i.m. at 4.4 mg/kg once daily (s.i.d.) or twice daily (b.i.d.) for 7 days. Concentrations of lactic dehydrogenase (LDH), lysozyme (LZM), alkaline phosphatase (AP), and glutamate dehydrogenase (GD) were measured as total 24‐h excretions. The s.i.d. regimen produced only a slight increase in LDH excretion after 5 days, whereas the b.i.d. regimen caused an increase in the excretion of all enzymes. The greatest elevations were observed for LZM and LDH. Of the enzymes studied, these appeared to be the most appropriate to monitor for potential nephrotoxicity, except that urinary concentrations did not correlate well with duration of gentamicin administration. Only slight elevations in BUN were observed for either regimen. Single daily administration increased urine osmolality slightly, but b.i.d. treatment caused a marked and immediate decrease in urine osomolality, [Na], and total Na excretion. Urinary [K] was also depressed, as was total K excretion after 6 days. Urine pH was not substantially affected. This study showed that the recommended daily dose of 4.4 mg/kg produced little if any evidence of nephrotoxicity as indicated by the parameters measured. Twice daily dosing, however, produced elevations in urine enzyme concentrations, and markedly decreased urine osmolality and Na and K excretion. Compared to other species studied, the cat appears particularly sensitive to urine concentrating alterations resulting from repeated gentamicin administration.
Radioimmunoassay of the anabolic agent zeranol. III. Zeranol concentrations in the faeces of steers implanted with zeranol (Ralgro)
Authors: DIXON S. N. , MALLINSON C. B.
Published: April 2008

Using a monoclonal antibody raised against zeranol, a radioimmunoassay has been validated for the determination of zeranol residues in the faeces of treated steers. The limit of decision defined as the mean apparent concentration of zeranol in the faeces of untreated cattle + 3 SD was 1 ng/g faeces. In a trial in which 27 steers were implanted with zeranol (36 mg) at the base of the ear and six steers were sham implanted, the mean maximum concentration of zeranol in faeces was 5.8 ng/g on Day 15 following implanting, declining to 1.67 ng/g on Day 34 following implanting. During this period there was a marked variation between animals sampled on the same day following implanting. At no time during the trial did the apparent concentration of zeranol in the faeces of untreated animals rise above 0.91 ng/g, which is below the limit of decision for this assay.
A chemiluminescent immunoassay for zeranol and its metabolites
Authors: JANSEN E. H.J. M. , BERG R. H. VAN DEN , ZOMER G. , ENKELAAR‐WILLEMSEN C. , STEPHANY R. W.
Published: April 2008

A sensitive immunoassay is presented for the detection of the xenobiotic oestrogenic growth promotor zeranol (Ralgro®) and the mycotoxin zearalanone. The detection is based on cheniiluminescence using a zeranol–isoluminol conjugate. A lowest detectable amount of 2–5 pg zeranol per tube was achieved. The bovine zeranol metabolites zearalanone and taleranol can also be determined, and this has been shown in a metabolic pilot study of zeranol in veal calves. This study indicates that taleranol is a major metabolite in male veal calves, in contrast to zearalanone which is known to be the major metabolite in adult cattle.
Effect of azaperone on cardiovascular responsiveness in stress‐sensitive pigs
Authors: GREGORY N. G. , WILKINS L.J.
Published: April 2008

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 deaths in pigs.
Clinical pharmacokinetics of flumequine in calves
Authors: ZIV G. , SOBACK S. , BOR A. , KURTZ B.
Published: April 2008

The minimal inhibitory concentration (MIC) of flumequine for 249 Salmonella, 126 Escherichia coli, and 22 Pasteurella multocida isolates 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 Cmax of 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 potential clinical value.
Chloramphenicol, lincomycin and oxytetracycline disposition in calves with experimental pneumonic pasteurellosis
Authors: BURROWS G. E. , BARTO P. B. , WEEKS B. R.
Published: April 2008

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two‐month‐old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant β for oxytetracycline was increased in calves with pneumonia from 0.0034 ± 0.0003/min to 0.0048 ± 0.0007/min between 2 h and 8 h. Thus the elimination half‐life in serum was shortened from 212.4 ± 20.3 min to 149.3 ± 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12‐h dose intervals with oxytetracycline.
Food Animal Residue Avoidance Databank (FARAD): a pharmacokinetic‐based information resource
Authors: SUNDLOF STEPHEN F. , CRAIGMILL ARTHUR C. , RIVIERE JAMES E.
Published: April 2008

The Food Animal Residue Avoidance Databank (FARAD) is a pilot project funded through the USDA Extension Service. It represents a major effort to compile into a single source large amounts of information on veterinary pharmaceutics, pharmacokinetics and physicochemical properties of drugs and other chemicals used in livestock production. FARAD is a computer‐based system consisting of five data and numerous command files that access the data files to facilitate rapid input and retrieval of the desired information. The data files include (1) proprietary information on all pharmaceutical products approved for use in food animals in the United States; (2) physicochemical information on more than 100 chemicals contained in the databank; (3) regulatory information pertaining to tolerance and action levels of chemical residues in animal products and allowable concentrations of drugs in feed; (4) pharmacokinetic rate and volume constants pertinent to residue depletion modeling in a variety of species; (5) bibliographic citations to which all of the information contained in the databank is referenced. All of the information in FARAD is currently available through three regional access centers in the United States, and direct computer access to the data may become available in the future.
Bioavailability of four slow‐release theophylline formulations in the Beagle dog
Authors: KORITZ G.D. , McKIERNAN B.C. , NEFF‐DAVIS C. A. , MUNSIFF I. J.
Published: April 2008

Theophylline was administered to six Beagles intravenously (Aminophyllin Injectable ®, Searle Laboratories) and orally as four sustained‐release formulations (Choledyl ®‐SA Tablets, Parke‐Davis; Theo‐Dur® Tablets, Key Pharmaceuticals; Theo‐24® Capsules, Searle Laboratories, and Slo‐bid Gyrocaps®, William H. Rorer, Inc.). Values were determined for mean residence time, mean absorption time, absolute bioavailability, time to peak plasma concentration, and peak plasma concentration normalized to a theophylline dose of 20 mg/kg. In this order the values found for each formulation were: Choledyl (10.2 ± 1.8 h, 2.8 ± 2.2 h, 63 ± 10%, 3.9 ± 1.0 h, 10 ± 1.1 μg/ml), Theo‐Dur (12.1 ± 5.2 h, 4.9 ± 5.3 h, 76 ± 18% 4.7 ± 3.1 h, 12 ± 3.7 μg/ml), Theo‐24 (15.6 ± 8.9 h, 8.1 ± 8.4 h, 30 ± 16%, 3.6 ± 1.7 h, 3.5 ± 1.3 μg/ml), and Slo‐bid (11.9 ± 1.9 h, 4.4 ± 1.3 h, 60 ± 9%, 4 ± 1.1 h, 8.6 ± 0.8 μg/ml). Choledyl, Theo‐Dur and Slo‐bid appear to have absorption characteristics which, if given twice daily, would maintain therapeutic plasma concentrations of theophylline between 10 and 20 M‐g/ml in the dog. Of these, Theo‐Dur was predicted to provide the least peak:trough fluctuation in theophylline plasma concentrations.
DDAVP‐induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs
Authors: JOHNSON G. S. , KRAUS. K. H. , TURRENTINE M. A. , DEAN P. W.
Published: April 2008

Johnson, G.S., Kraus, K.H., Turrentine, M.A. & Dean P.W. DDAVP‐induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs. J. vet. Pharmacol. Therap. 9, 370–375.

Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1–2.0 ng DDAVP per kg body weight induced dose‐dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor. Plasma concentrations of von Willebrand factor (determined antigenically as factor VHI‐related antigen and functionally as coagglutinin cofactor activity) and coagulation factor VIII were measured immediately before and at 10, 30, and 120 min after 10‐min intravenous infusions of DDAVP. The greatest increases in coagulation factor VIII were produced with the 2.0 μg/kg dose. Ten minutes after infusion the mean increase in coagulation factor VIII was 32 units/dl (concentrations of all indices were reported relative to concentrations in a standard canine plasma pool, arbitrarily assigned a concentration of 100 units/dl) and this increase did not change significantly throughout the duration of the experiment. At 10 min post‐infusion, the mean factor VHI‐related antigen concentration increased 81 units/dl (dose = 2.0 μg/kg) and did not change significantly for the duration of the experiment. The maximum mean increase in coagglutinin cofactor activity, 141 units/dl, occurred 10 min after infusion (dose = 1.0 μg/kg). Coagglutinin cofactor activity decreased significantly from peak activity by 120 min post‐infusion
Clinical evaluation of R 51163, a new sedative in cattle
Authors: DEGRYSE A.‐D. , OOMS L. A. A.
Published: April 2008

Degryse, A.‐D. & Ooms, L. A. A. Clinical evaluation of R 51163, a new sedative in cattle. J. vet. Pharmacol. Therap. 9, 376–384.

R 51163, a purine alkyl piperidine derivative, has been shown to produce reliable sedation in cattle of varying age and breed in three different types of experiments: transport and regrouping of cattle which had only been handled occasionally; manipulations and minor interventions; minor and major surgery with or without supplementary local anaesthesia. With dose rates of R 51163 at 0.05 mg/kg i.v. and of 0.10‐0.15 mg/kg i.m. sedation became prominent within 10–15 min and lasted at least 60 min. Caesarian sections were performed under adequate sedation with R 51163 with dose ranging from 0.018 to 0.05 mg/kg i.v. and from 0.075 to 0.10 mg/kg i.m. The data suggest possible increased responsiveness to the drug at the time of calving.
The lack of effect of inoculation with equine influenza vaccine on theophylline pharmacokinetics in the horse
Authors: SHORT C. R. , HORNER M. W. , BLAY. P. K. S. , MOSS. M. S. , EDINGTON N. , CLARKE C.R.
Published: April 2008

Short, C.R., Horner, M.W., Blay, P.K.S., Moss, M.S., Edington, N. & Clarke, C.R. The lack of effect of inoculation with equine influenza vaccine on theophylline pharmacokinetics in the horse. J. vet. Pharmacol. Therap. 9, 426–432. 1986.

Several studies conducted during the past few years have shown that the pharmacokinetics of a variety of drugs may be altered following viral infection or vaccination. The elimination of drugs which are extensively metabolized, such as theophylline, may be prolonged, especially following exposure to RNA viruses such as Type A influenza or similar orthomyxoviruses. The purpose of this study was to determine whether vaccination of horses with equine influenza virus affected pharmacokinetic parameters describing the distribution and elimination of intravenously administered theophylline. Three thoroughbred horses and three ponies were vaccinated with a trivalent vaccine containing inactivated strains of A/Equi 1 (Prague), A/Equi 2 (Miami) and A/Equi 2 (Kentucky 81). Antibody titre, serum interferon concentrations, and the pharmacokinetic parameters t½β, Vc, Vd(ss), Vd(area) and C/B were measured at various intervals after vaccination. Antibody titre increased substantially in only two animals, while plasma interferon was detectable in low concentrations in four subjects. There was no significant change in any parameter describing the pharmacokinetics of theophylline when measured 2, 6, or 12 days after vaccination. It is suggested that the failure of vaccination to substantially increase plasma interferon concentrations, and thereby alter theophylline elimination, was related to the use of an inactivated viral vaccine, the only type available for vaccination of horses against infection with equine influenza. Regular use of such vaccines, as is required by most Racing Authorities, is therefore unlikely to affect drug withdrawal times.
Field evaluation of the oxfendazole pulse release bolus for the chemoprophylaxis of bovine parasitic gastroenteritis: a comparison with three other control strategies
Authors: JACOBS D.E. , FOX M.T. , COWLING G. , FOSTER J. , PITT S. R. , GERRELLI D.
Published: April 2008

Jacobs, D.E., Fox, M.T., Cowling, C, Foster, J. Pitt, S.R. & Gerrelli, D. Field evaluation of the oxfendazole pulse bolus for the chemoprophylaxis of bovine parasitic gastroenteritis: a comparison with three other control strategies. J. vet. Pharmacol. Therap. 10, 30–36.

Three trials were conducted in southern England involving 120 autumn‐born calves to evaluate the ability of an oxfendazole pulse‐release intraluminal device (OPRB) to control parasitic gastroenteritis (PGE). Matched groups were set‐stocked on adjacent paddocks. One group received an OPRB at turn‐out; one was treated with an alternative chemoprophylactic programme; while the third acted as an untreated control. In each trial clinical PGE occurred in the latter group but not in OPRB or alternative strategy groups. The OPRB, the morantel sustained release bolus (MSRB) and fenbendazole administered at 3 and 6 weeks after turn‐out gave similar weight‐gain benefits when compared with untreated controls (P < 0.01), but the growth rate of animals given regular levamisole treatments from July to housing was significantly poorer than the matching OPRB group (P < 0.05) although better than controls. Faecal egg‐output of OPRB calves was reduced by 97.0–99.9% compared with 95.5 and 58.9% for MSRB and fenbendazole treatments. Consequently, the late summer/ autumn peaks in pasture larval counts were considerably reduced in all treatment groups other than the late‐season levamisole strategy which reduced overall egg‐output by only 37.6%. Serum pepsinogen and gastrin values confirmed a greater degree of abomasal disturbance in calves grazing on the more highly contaminated pastures. Incidental lungworm infections became clinically apparent in the control groups of two trials but not in any OPRB or alternative treatment group.
The release of insoluble antibiotics from collagen ocular inserts in vitro and their insertion into the conjunctival sac of cattle
Authors: PUNCH P. I. , COSTA N. D. , EDWARDS M.E. , ] G. E. WILCOX
Published: April 2008

Punch, P.I., Costa, N.D., Edwards, M.E. & Wilcox, G.E. The release of insoluble antibiotics from collagen ocular inserts in vitro and their insertion into the conjunctival sac of cattle. J. vet. Pharmacol. Therap. 10, 37–42.

The release rate of procaine penicillin, erythromycin and erythromycin estolate from soluble and insoluble collagen films was investigated in vitro to develop an ocular insert for the treatment of infectious bovine keratoconjunctivitis. The release rate and duration of release varied according to the selection of antibiotic and vehicle. The combination of erythromycin estolate and soluble collagen produced the most sustained drug‐delivery system. However, due to the inappropriate physical properties of collagen and poor retention of ocular inserts, it was considered that the development of an antibiotic‐impregnated collagen ocular insert requires further investigation.
Antipyrine disposition in calves. I. Effects of some drugs
Authors: DEPELCHIN B. O. , BLODEN S. , ANSAY M.
Published: April 2008

Depelchin, B.O., Bloden, S. & Ansay, M. Antipyrine disposition in calves. I. Effects of some drugs. J. vet. Pharmacol. Therap. 10, 49–53.

The influence of four drugs on antipyrine pharmacokinetic parameters was studied after 3 h, 2 and 6 days in 32 Friesian calves. Dexamethasone phosphate and griseofulvin led to increased antipyrine elimination. The effect of dexamethasone remained significant 2 and 6 days later. The rate of antipyrine elimination was markedly but transiently depressed by chloramphenicol and oxytetracycline. The apparent volume of antipyrine distribution remained unaltered during treatment.
Clavulanate‐potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves
Authors: SOBACK S. , BOR A. , KURTZ B. , PAZ R. , ZIV G.
Published: April 2008

Soback, S., Bor, A., Kurtz, B., Paz, R. & Ziv, G. Clavulanate‐potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves. J. vet. Pharmacol. Therap.10, 105–113.

The minimal inhibitory concentrations (MIC) of amoxycillin and clavulanate‐potentiated amoxycillin (amoxycillinxlavulanic acid, 4:1 by weight) were compared for 171 Salmonella, 170 Escherichia coli, and 32 Pasteurella isolates recovered from infected neonatal calves. In the presence of clavulanic acid, the MIC of amoxycillin was reduced to levels ≥ 12.5 μg/ml for all the Salmonella group B, all the Pasteurella, and for 12 out of the 44 E. coli isolates which were resistant to amoxycillin (MIC ≥ 100.0 μg/ml). For isolates sensitive to amoxycillin (MIC ≥ 1.56 μg/ml) there was no change in MIC values in the presence of clavulanic acid. A small proportion of Salmonella and E. coli isolates were resistant to clavulanate‐potentiated amoxycillin. In a cross‐over trial involving 10 preruminant (2 weeks old) calves, amoxycillin trihydrate and clavulanate‐potentiated amoxycillin were administered orally at 10 mg/kg. An analysis of serum amoxycillin level data showed that the pharmacokinetic parameters t½ab, Cmax, t½β, AUC, Cpo, and f (estimated drug absorption ratio) were the same after treatment with amoxydrate and clavulanate‐potentiated amoxycillin. Administration of clavulanate‐potentiated amoxycillin and probenecid resulted in elevation and prolongation of serum amoxycillin levels. Computations showed that in preruminant calves serum amoxycillin concentrations sufficient to inhibit sensitive pathogens can be maintained by oral clavulanate‐potentiated amoxycillin treatment at 10 mg/kg TID. At two times that dose rate serum drug concentrations capable of inhibiting 50% of all types of pathogens examined can be maintained. Amoxycillin was apparently inactivated by the g.i. contents of early ruminant (6 weeks old) calves as oral clavulanate‐potentiated amoxycillin treatment at 20 mg/kg did not result in serum drug levels of potential therapeutic value.
Effect of organic vehicles on the pharmacokinetics of aminophylline administered intravenously to goats
Authors: DAVIS L. E. , NEFF‐DAVIS CAROL A. , KORITZ G. D. , BEVILL R. F. , SHARMA G. C. , LANGSTON V. C. , MUNSIFF IRENE J.
Published: April 2008

Davis, L.E., Neff‐Davis, C.A., Koritz, G.D., Bevill, R.F., Sharma, G.C., Langston, V.C. & Munsiff, I.J. Effect of organic vehicles on the pharmacokinetics of aminophylline administered intravenously to goats.J, vet. Pharmacol. Therap. 10, 144–149.

Aminophylline dissolved in water, propylene glycol, or dimethyl sulfoxide was administered intravenously to goats in a randomized cross‐over experiment. Model‐dependent and model‐independent pharmacokinetic parameters for theophylline were compared on the basis of the solvent used in the dosage form administered. No difference was found in any pharmacokinetic parameter. Thus, we found no evidence for the possibility that the organic solvents studied would confound pharmacokinetic investigations of theophylline and similar lipophilic drugs.
Concentrations of immunoreactive leukotriene B4 in uterine lavage fluid from mares with experimentally induced and naturally occurring endometritis
Authors: WATSON E. D. , STOKES C. R. , BOURNE F.J.
Published: April 2008

Watson, E.D., Stokes, C.R. & Bourne, F.J. Concentrations of immunoreactive leukotriene B4 in uterine lavage fluid from mares with experimentally induced and naturally occurring endometritis. J. vet. Pharmacol. Therap.11, 130–134.

Acute endometritis was induced in ovariectomized pony mares by infusion of a 1% solution of oyster glycogen. Maximum concentrations of immunoreactive leukotriene B4 in uterine washings coincided with the greatest rate of infiltration of neutrophils into the uterine lumen. Concentrations of immunoreactive leukotriene B4 decreased to basal levels 6 h after infusion and were unaffected by administration of ovarian steroids to ovariectomized mares. Uterine washings from mares with persistent endometritis did not contain significantly different concentrations of leukotriene B4 from genitally normal mares.
Vasoactive intestinal peptide (VIP), a putative neurotransmitter of nonadrenergic, noncholinergic (NANC) inhibitory innervation and its relevance to therapy
Authors: VENUGOPALAN C.S.
Published: April 2008

Nonadrenergic, noncholinergic (NANC) innervation, the third division of the autonomic nervous system, has both inhibitory and excitatory parts. The excitatory part received only limited attention. Substance P has been suggested to be the neurotransmitter of the excitatory part. The NANC‐inhibitory innervation has recently been studied in detail. Although the neurotransmitter has not been conclusively identified, a substantial body of evidence exists to support vasoactive intestinal peptide (VIP) as the neurotransmitter. VIP is widely distributed in the body. Reports show that this innervation in animals and man plays a significant role in both health and disease. Pathological conditions could result from either an increase or decrease in VIP production. An absence of VIP‐producing neurons has been identified to be responsible for Hirschsprung's disease in the alimentary system and hyperactive airways in the respiratory system. An increase in VIP production is associated with chronic water diarrhea syndrome in humans. Taking these factors into consideration, various therapeutic measures are suggested with the use of VIP or its antagonists.
Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus)
Authors: GRONDEL J.L. , NOUWS J. F. M. , SCHUTTE A. R. , DRIESSENS F.
Published: April 2008

Grondel, J.L., Nouws, J.F.M., Schutte, A.R. & Driessens, F. Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus). J. vet. Pharmacol. Therap.12, 157–162.

A comparative pharmacokinetic study was conducted in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus) following intravenous (i.v.) and intramuscular (i.m.) administration of oxytetracycline (OTC) at a dose rate of 60 mg/kg body weight. Trout and catfish were kept in aerated tap water in tanks at constant temperatures of 12°C and 25°C, respectively. The two‐ and three‐compartment open models adequately described plasma drug disposition in African catfish and rainbow trout respectively, following i.v. OTC administration. Compared to catfish (Cop= 86 ± 10 μg/ml) an eightfold higher extrapolated zero time concentration was obtained in trout (Cop= 753 ± 290 μg/ ml). A significant difference was observed with respect to the relatively large apparent distribution volumes (Vd(area)) after i.v. OTC administration (trout, mean value: 2.1 l/kg; catfish, mean value: 1.3 l/kg). The mean final elimination half‐lives of both fish species were greater than previously reported in mammals (trout, 89.5 h; catfish, 80.3 h). A mean maximum plasma concentration (Cmax = 56.9 μg/ml) was obtained in trout at 4 h after i.m. administration of OTC. In catfish a lower Cmax of 43.4 (μg/ml was determined at about 7 h. No significant difference was observed with respect to bioavailability following i.m. administration of OTC (trout, 85%; catfish, 86%).
The effects of salbutamol on blood pressure and heart rate in Large White and Pietrain‐cross breeds of pig
Authors: WHITE D. G. , ROLPH T. P. , WAGSTAFF A.J.
Published: April 2008

The effects of the β2‐agonist salbutamol, on pig heart rate and blood pressure were evaluated at the expected commercially used concentration of 3 ppm in final feed, and at three times this level. Salbutamol was administered to pigs previously fed on control diet (‘naive’), and in a second study to pigs fed 3 ppm salbutamol for 19 days (‘acclimatized’). Heart rate and blood pressure were measured in conscious 30 kg pigs before (pre‐ingestive), during (ingestive) and after ingestion (absorptive) of feed containing 3 or 9 ppm salbutamol. To assess any interaction with ‘stress genotype’ pigs, measurements were performed in Large White and Pietrain‐cross breeds. The mean preingestive heart rates for the Large White and Pietrain‐cross pigs were 127 and 109 beats/min, respectively. The corresponding figures for mean arterial blood pressure were 121 and 122 mmHg. The act of ingesting control feed caused heart rate to rise by 36–39% and blood pressure to increase by 17–27%. During the absorptive phase for ‘naive’ pigs fed 3 ppm salbutamol in the diet, blood pressure fell 5–11% and heart rate increased 20–24%, reflecting a classical baroreceptor mediated response. At 9 ppm the fall in blood pressure of 5–11% was similar to that at 3 ppm, while the rise in heart rate was larger at 31–38%. The magnitude of the changes at both 3 and 9 ppm was less than that evoked by the act of ingestion, with the exception of the heart rate response in Large Whites at 9 ppm, which was similar. The responses of the two breeds were comparable, indicating that salbutamol is unlikely to exacerbate the cardiovascular responses seen in potentially stress‐susceptible pigs. The acute changes elicited by 3 ppm salbutamol during the absorptive phase in ‘naive’ pigs were abolished or substantially less in acclimatized pigs, implying a tachyphylaxis to the agonist's actions. This was confirmed by 9 ppm of salbutamol increasing heart rate of ‘acclimatized’ Large Whites to the same degree as 3 ppm in ‘naive’ counterparts. The desensitization in Pietrain‐cross pigs was even more marked with no increase in heart rate produced by 9 ppm salbutamol following acclimatization. These data, combined with the rapid tachyphylaxis of response, indicate that salbutamol at the intended commercial inclusion of 3 ppm will not compromise the cardiovascular stability of the growing pig at rest.
The effects of a β2‐agonist (clenbuterol), and anti‐bacterial drugs (trimethoprim with sulphadiazine; oxytetracycline) on calf mucociliary clearance
Authors: DAVIES C. P. , WEBSTER A.J. F.
Published: April 2008

A non‐invasive radio‐aerosol technique was employed to study mucociliary clearance patterns in three groups of four calves of different ages. The initial clearance pattern, the percentage cleared in 1 h, and the percentage cleared between 1 and 19 h were used as indices of clearance efficiency. (Percentage retention at 19 h was used as an index of alveolar deposition.) These measurements were recorded in a series of experiments designed to investigate the effects of: clenbuterol (given as a single intravenous injection, 0.75 (i.g/kg); a combination of trimethoprim and sulphadiazine‐TMPS (administered by intramuscular injection twice daily for 3 days: 2.5 mg/kg trimethoprim; 12.5 mg/ kg sulphadiazine) alone, or with a supplementary injection of clenbuterol; and oxytetracycline (administered by intramuscular injection twice daily for 3 days; 3 mg/kg). Clenbuterol alone tended to increase clearance rate, although this effect did not achieve statistical significance. The combination of TMPS with clenbuterol produced results similar to those of clenbuterol alone. Neither TMPS nor oxytetracycline had any significant effect on indices of mucociliary clearance. Differences were observed between calves of different age groups, particularly in clearance phases between 1 and 19 h.
Chlortetracycline in swine‐bioavailability and pharmacokinetics in fasted and fed pigs
Authors: KILROY C. R. , HALL W. F. , BANE D. P. , BEVILL R. F. , KORITZ G. D.
Published: April 2008

Chlortetracycline hydrochloride was administered intra‐arterially (11 mg/kg) and as an oral drench (33 mg/kg) to ten 21.0‐31.5‐kg pigs. Five of the pigs were fasted 18 h prior to dosing and five of the pigs were fed ad libitum prior to dosing. The mean volume of distribution determined by area‐under‐the‐curve calculations for the fasted pigs (0.967 ± 0.210 1/kg) was significantly less (P < 0.05) than the mean volume of distribution for the fed pigs (1.39 ± 0.31 1/kg). Mean total body clearance of the drug was also significantly less (P < 0.05) in the fasted pigs (0.165 ± 0.055 1/kg/h) as compared to the fed pigs (0.307 ± 0.053 1/kg/h). The elimination constants (ß) were not found to be statistically different (P < 0.05): 0.1811 ± 0.0057 for the fasted pigs; 0.2260 ± 0.0461 for the fed pigs. The bioavailability for both groups was similar; 19.12 ± 8.3% for the fasted pigs and 17.88 ± 5.3% for the fed pigs.

In a second experiment three groups of six pigs which weighed 34.5‐44.1 kg were fed a corn‐soy diet ad libitum. The rations were fortified with chlortetracycline at 100, 400 or 1000 mg chlortetracycline hydrochloride/kg feed. Chlortetracycline concentrations were determined in plasma samples collected over a 6‐day period. Plasma chlortetracycline concentrations reach a plateau within 24 h after initial access to the trial diets and were highly correlated with the dose of the drug consumed (r2= 0.97).
The pharmacokinetics of chloramphenicol in plasma and saliva of dairy cows
Authors: DOTTER A. , KROKER R. , ARNOLD D.
Published: April 2008

In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio‐immunoassay, requires only small sample volumes, no further clean‐up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open‐compartment models, and to compare it with the results of previous studies. The radio‐immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas‐chromatographic method with electron‐capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk‐producing animals.
The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog
Authors: VÄHÄ‐VAHE A.T.
Published: April 2008

Vähä‐Vahe, A.T. The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog. J. vet. Pharmacol. Therap. 13, 198–205.

The efficacy of atipamezole, a recently introduced α2‐adrenoceptor antagonist, in reversing medetomidine‐induced effects in dogs was investigated in a clinical study. Dogs from eight Finnish small‐animal hospitals were sedated with a 40‐μg/kg dose of the α2‐agonist medetomidine i.m. In the first part of the study (n=319), a randomized, double‐blind design with respect to the dose of atipamezole (0, 80, 160 and 240μg/kg i.m.) was used. In a separate study (n=358), which was an open trial, the selected dose of atipamezole was 200μg/kg i.m. Atipamezole at dose rates of 80–240μg/kg rapidly and effectively reversed medetomidine‐induced deep sedation‐analgesia, recumbency and bradycardia. The median arousal time after atipamezole was 3–5 min, and walking time was 6–10 min compared to >30 min for both effects after placebo. Heart rate also increased in a dose‐related manner after atipamezole administration. The investigators' overall evaluation of the ability of atipamezole to reverse the effects of medetomidine was ‘good’ in 90%, and ‘moderate’ in 9% of cases. Relapse into sedation was reported in three individual cases. Side‐effects were minimal. It is concluded that at doses four‐to sixfold the medetomidine dose, atipamezole is a highly effective and safe agent in reversing medetomidine‐induced sedation‐analgesia, recumbency and bradycardia in dogs in veterinary practice.

A. T. Vähä‐Vahe, Farmos Group Ltd., Research Center, PO Box 425, SF‐2010I Turku, Finland.
Comparative benzylpenicillin pharmacokinetics in the dromedary Camelus dromedarius and in sheep
Authors: OUKESSOU M. , HOSSAINI J. , ZINE‐FILALI R. , TOUTAIN P. L.
Published: April 2008

Oukessou, M., Hossaini, J., Zine‐Filali, R. & Toutain, P.L. Comparative benzylpenicillin pharmacokinetics in the dromedary Camelus dromedarius and in sheep. J. vet. Pharmacol. Therap. 13, 298–303.

Benzylpenicillin pharmacokinetics were compared in the dromedary Camelus dromedarius (n=5) and in sheep (n=5) after administration of a single intravenous injection of benzylpenicillin. The data were described by an open three‐compartment model with elimination from the central compartment. Body clearance (Clb) was 4.87±0.63 ml/min/kg in the dromedary and 9.17±1.39 ml/min/kg in sheep, the steady‐state volumes of distribution (Vss) were 0.151±0.023 l/kg and 0.165±0.038 l/kg and the mean residence times (MRT) 27.34±1.38 min and 14.95±4.16 min in the dromedary and in sheep, respectively. It was concluded that benzylpenicillin elimination occurs more slowly in the dromedary dian in sheep and that use of the same dosage regimen for the two ruminant species may lead to significant differences in plasma concentrations and therapeutic efficacy.

P. L. Toutain, INRA Station de Pharmacologie‐Toxicologie, 180 chemin de Tournefeuille, Toulouse, France.
The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs
Authors: PIJPERS A. , SCHOEVERS E.J. , van GOGH H. , van LEENGOED L. A. M. G. , VISSER I. J. R. , van MIERT A. S. J. P. A. M. , VERHEIJDEN J. H. M.
Published: April 2008

Pijpers, A., Schoevers, E.J., van Gogh, H., van Leengoed, L.A.M.G., Visser, I.J.R., van Miert, A.S.J.P.A.M. & Verheijden, J.H.M. The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs. J. vet. Pharmacol. Therap. 13, 320–326.

The pharmacokinetics of oxytetracycline (OTC) were studied in healthy pigs and in pigs endobronchially inoculated with Actinobacillus pleuropneumoniae toxins. In two groups of seven pigs OTC was administered intravenously in a single dose of 10 or 50 mg/kg, respectively. OTC was administered to clinically healthy pigs and 7 days later at 3 h after a challenge with A. pleuropneumoniae toxins. Pneumonia developed in toxin‐treated pigs. In the challenged pigs there was a decreased distribution‐rate constant (α) and a significantly increased elimination‐rate constant (ß) (P<0.05). Moreover, the apparent volume of distribution (Vdß) was decreased. The elimination half‐lives (t1/2ß) were approximately 6 h in the healthy pigs and 5 h in the diseased animals. There was no difference in the pharmacokinetic profile of OTC following administration of 50 mg/kg compared to 10 mg/kg.

A. Pijpers, Department of Herd Health and Reproduction, PO Box 80.151, 3508 TD Utrecht, The Netherlands.