bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical pharmacology of mecillinam in calves
Authors: SOBACK S. , BOR A. , PAZ R. , ZIV G.
Published: April 2008

Soback, S., Bor, A., Paz, R. & Ziv, G. Clinical pharmacology of mecillinam in calves. J. vet. Pharmacol. Therap. 9, 385–393.

The minimal inhibitory concentrations (MIC) of mecillinam, a novel β‐amidinopenicillanic acid derivative with unusual activity against Gram‐negative bacteria, were compared with the MIC of cephazolin, cephalothin, amoxycillin, oxytetracycline, chloramphenicol, dihydrostreptomycin, neomycin, kanamycin, gentamicin and sulfadoxin/trimethoprim (TMP) against pathogenic Gram‐negative bacteria recovered from neonatal calves. The MIC values of mecillinam ranged between 0.05 μg/ml and 12.5 μg/ml, and the MIC90values were 1.56 μg/ml and 3.12 μg/ml. The activity of mecillinam against salmonella,Escherichia coliandPasteurella multocidawas similar to or slightly greater than the activities of the first‐generation cephalosporins, gentamicin and sulfa/TMP. Mecillinam concentrations ≤ 3.12 μg/ml inhibited the growth of the majority of isolates which were resistant (MIC90 > 100 μg/ml) to the other antibiotics studied. The minimum bactericidal concentration (MBC) values of mecillinam were two‐ to three‐fold higher than the MIC values.

The two‐compartment open model was appropriate for the analysis of serum mecillinam concentrations measured after intravenous administration. The distribution half‐life (t½α) was 11.7 min, the elimination half‐life (t½β) was 53.3 min, and the apparent volume of distribution (Vd(area)) and the distribution volume at steady state (Vd(ss)) were 0.568 and 0.896 1/kg, respectively. The drug was quickly absorbed after intramuscular (i.m.) injection; peak serum drug concentrations were directly related to the dose administered. They were obtained 30 min after treatment and the i.m.t½was approximately 65 min. An aqueous solution of probenecid administered i.m. at 40 mg/kg together with mecillinam resulted in peak serum drug concentrations which were nearly twice the peak observed after the i.m. administration of mecillinam alone and during the first 2 h after treatment the i.m.t½of mecillinam was 110 min.

Mecillinam was approximately 25% bound to serum proteins. The duration of free drug concentrations in the tissues after i.m. administration were estimated from the serum drug level data,Vd(ss),t½and the MIC. Computations showed that mecillinam should be administered at 16 mg/kg every 5 h, and with the co‐administration of probenecid the dosage interval can be extended to 6.5 h, in order to maintain effective drug concentrations potentially sufficient to inhibit 90% of the salmonella,E. coli, andP. multocidaisolates in tissues.
Bioavailability and pharmacokinetics of ampicillin and amoxycillin from tablets, capsules and long‐acting preparations in the homing pigeon (Columba livia)
Authors: DORRESTEIN G. M. , GOGH H. VAN , RINZEMA J. D. , BUITELAAR M. N.
Published: April 2008

Dorrestein, G.M., van Gogh, H., Rinzema, J. D. & Buitelaar, M.N. Bioavailability and pharmacokinetics of ampicillin and amoxycillin from tablets, capsules and long‐acting preparations in the homing pigeon (Columba livia). J. vet. Pharmacol. Therap. 9, 394–401.

Three ampicillin and three amoxycillin formulations (tablets and capsules, administered orally, and oily suspensions, injected intramuscularly (i.m.) and subcutaneously (s.c.)) were studied in twenty adult homing pigeons (Columba livia). Bioavailability, pharmacokinetics and recovery were determined for each product and administration route. A standard dose of 50 mg/pigeon or 100 mg/kg was used in each study. The mean availability calculated for each of these preparations was 7% for ampicillin anhydrate tablets, 22% for amoxycillin trihydrate tablets, 17% for ampicillin trihydrate capsules, 67% for amoxycillin trihydrate capsules, 46% for ampicillin oily suspension i.m., 67% for amoxycillin oily suspension i.m. and 43% for amoxycillin oily suspension s.c. The blood concentration–time curves for the tablets were very scattered, which was far less the case for the capsules. The maximum blood concentration (Cmax) for amoxycillin was twice as high as for ampicillin. The Cmax resulting from the oily suspensions administered i.m. were low (4.35 ± 1.05 and 5.04 ± 1.36 mg/1, for ampicillin and amoxycillin, respectively). The rmax for ampicillin was 10 h and for amoxycillin it was 0.9 h after administration. Both curves showed biphasic absorption, the initial peak representing an absorption and a distribution phase and the second part reflecting the ‘depot‐nature’ of the drug. After the s.c. administration of the amoxycillin oily suspension the same pattern was found, but the Cmax, which was found at 2.13 ± 1.03 h after administration, was low (2.81 ± 0.68 mg/1). The duration of potentially therapeutic blood concentrations after administration of each preparation for the MIC levels of 0.5 and 2.5 mg/1 are also presented.
Oral treatment of polioencephalomalacia and subclinical thiamine deficiency with thiamine propyl disulphide and thiamine hydrochloride
Authors: THOMAS K.W
Published: April 2008

Thomas, K.W. Oral treatment of polioencephalomalacia and subclinical thiamine deficiency with thiamine propyl disulphide and thiamine hydrochloride. J. vet. Pharmacol. Therap. 9, 402–411.

Thiaminase type 1 production by Bacillus thiaminolyticus and activity in vitro were repressed by the primary substate thiamine and by thiamine monophosphate and thiamine propyl disulphide. At thiamine concentrations of 300–3000 μmol/1 production of active enzyme by B. thiaminolyticus, and activity of purified enzyme, were totally repressed. Growth of B. thiaminolyticus was inhibited by thiamine propyl disulphide at 3000 μmol/1. Activity of purified thiaminase was lost when incubated with ruminal fluid from healthy thiaminase free sheep. Enzyme activity was also lost when exposed to mildly alkaline conditions but was stimulated and stabilized against heat denaturation if treated with dithiothreitol.

Thiaminase activities in the ruminal fluids of cases of ovine polioencephalomalacia were repressed within 2 h of oral administration of thiamine propyl disulphide. Blood pyruvate levels and transketolase activities were restored to normal following treatment. Treated animals recovered clinically and were returned to pasture.
Depression of reticulo‐ruminal motor functions through the stimulation of 012‐adrenoceptors
Authors: RUCKEBUSCH Y. , ALLAL C.
Published: April 2008

Ruckebusch, Y. & Allal, C. Depression of reticulo‐ruminal motor functions through the stimulation of α2‐adrenoceptors. J. vet. Pharmacol. Therap. 10, 1‐10.

Inhibition of the cyclical contractions of the reticulum and the rumen by detomidine (10–40 (μg/kg, i.v.), xylazine (20–80 μg/kg, i.v.) and clonidine (2.5–10 μg/kg, i.v.) were compared in sheep and cattle housed individually in box stalls. Two (X2‐adrenergic receptor blocking agents, tolazoline and yohimbine, were administered intravenously for prevention (0.1‐0.4 mg/kg) or reversal (0.4‐1.2 mg/kg) of these effects. Continuous recording of the reticulo‐ruminal contractions and measurement of the volume of ruminal gas eliminated through the upper respiratory tract indicated that the three a2‐agonists inhibited the primary ruminal contractions associated with the reticular contractions. The occurrence of secondary ruminal contractions was also blocked in sheep, but only suppressed in cattle. The inhibition of reticulo‐ruminal contractions was prevented or reversed competitively by the two ct2‐blocking agents, suggesting an ci2‐adrenoceptor mediation of the inhibition of cyclical motor activity of the reticulo‐rumen. In contrast with tolazoline, yohimbine was unable to alleviate the accumulation of gas resulting from inhibition of the secondary ruminal contractions.
Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves
Authors: SOBACK S. , KURTZ B. , ZIV G.
Published: April 2008

Soback, S., Kurtz, B. & Ziv, G. Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves. J. vet. Pharmacol. Therap. 10, 17–22.

Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre–ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half–life (t1/2β) was 34 min and the apparent volume of distribution at steady–state (Vd ss) was 0.30 I/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 μ/ml, 1.06 μ/ml and 2.14 μ/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co–administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8%± 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6–week–old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg.

In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.
Control of Toxocara cants in puppies: a comparison of screening techniques and evaluation of a dosing programme
Authors: JACOBS D.E.
Published: April 2008

Jacobs, D.E. Control of Toxocara cards in puppies: a comparison of screening techniques and evaluation of a dosing programme. J. vet. Pharmacol. Therap. 10, 23–29.

Conventional chemoprophylaxis of canine toxocariasis is based upon the treatment of young puppies. It is proposed that physiological considerations and the complexity of the host–parasite relationship in the case of Toxocara canis demand that anthelmintic evaluation should properly be conducted in such animals rather than in adolescent or adult dogs. A screening model using the critical trial technique in early weaned pups gave variable results even with compounds known to be of high efficacy in older dogs. Circumstantial evidence suggested that this inconsistency may be related to the rate of passage of ingesta through such young animals. More satisfactory results were obtained by pairing unweaned naturally infected puppies by weight and sex and treating one of each pair with the test compound. Natural in utero and transmammary infection was found to give fairly consistent worm‐burdens within each litter and a good indication of efficacy could therefore be estimated by comparing post mortem worm‐counts. On this basis, the apparent efficacies of pyrantel pamoate (5 mg kg‐1) and piperazine (100 mg kg‐1) were found to be 83.5 and 82.5%, respectively. This method was extended to evaluate a prophylactic programme in which anthelmintic therapy was given to pups when aged 10, 20 and 30 days. Intestinal T. canis populations were reduced, at 35 days of age, by between 94.2% and 98.0%. This programme increased overall weight gains between 10 and 30 days of age by 18% (P < 0.05) although there was great variation between litters. The biggest response was observed in male pups between 20 and 30 days old.
Comparative pharmacokinetics of gentamicin, neomycin and oxytetracycline in newborn calves
Authors: BURROWS G. E. , BARTO P. B. , MARTIN B.
Published: April 2008

Burrows, G.E., Barto, P.B. & Martin, B. Comparative pharmacokinetics of gentamicin, neomycin and oxytetracycline in newborn calves. J. vet. Pharmacol. Therap. 10, 54–63.

The pharmacokinetics of three antibiotics – gentamicin, neomycin and oxytetracycline were determined in newborn calves. The kinetic determinations, using two‐compartment open models, were made at increasing ages from 1 day to 42 days and compared with those made from older calves (250+ days). Although all three antibiotics are eliminated unchanged primarily by glomerular filtration, there were marked differences in the development of elimination processes for individual drugs. The pharmacokinetics of neomycin were not influenced by age. Although the elimination half‐life of gentamicin appeared to decrease with age, the changes were not significant and were due to an increased elimination rate in only one calf. There was no change with age in the remaining three calves. Oxytetracycline elimination was significantly reduced in newborn calves. This was exemplified by a decrease in the half‐life of elimination t1/2(β) from 672.5 ± 99.4 in the newborn to 385.6 ± 76.8 at 6 weeks of age, and 377.3 ± 40.8 min in the 250‐day‐old calf. These changes were consistent in all four calves. The rate of elimination remained low for the first 4 weeks of life. The volume of distribution Vd, area was not changed after the first week of life. Based on pharmacokinetic changes, an adjustment of dosage is indicated for oxytetracycline in the newborn calf as compared to the older calf or adult.
Clinical, cardiovascular and respiratory effects of R8110 in premedicated dogs
Authors: DIJK P. van , DEGRYSE A.‐D. , OOMS L. , LAGERWEIJ E.
Published: April 2008

van Dijk, P., Degryse, A.‐D., Ooms, L. & Lagerweij, E. Clinical, cardiovascular and respiratory effects of R8110 in premedicated dogs. J, vet. Pharmacol. Therap. 10, 114–118.

The clinical, cardiovascular and respiratory effects after i.v. administration of R8110, a fluoro analogue of etomidate (Fig. 1), were studied in pre‐medicated dogs. The clinical observations were made at doses of 3 and 4 mg/kg body weight (BW) injected slowly i.v., whereas cardiovascular and respiratory studies were carried out at a dose rate of 3 mg/kg R8110 i.v. Induction and recovery were smooth and no significant side‐effects were observed. The cardiovascular system was slightly influenced, but respiration was hardly affected. The effect of pre‐medication on respiration and the cardiovascular system was hardly potentiated by R8110. Although there were significant changes in cardiovascular and biochemical parameters, all values remained within physiological limits. R8110 appeared to be a safe and reliable induction agent.
Evaluation of the potential for interference by dimethyl sulfoxide (DMSO) in drug detection in racing animals
Authors: CRAIG A. M. , BLYTHE L. L. , APPELL L. H. , SLIZESKI M. L.
Published: April 2008

Craig, A.M., Blythe, L.L., Appell. L.H. & Slizeski, M.L. Evaluation of the potential for interference by dimethyl sulfoxide (DMSO) in drug detection in racing animals. J. vet. Pharmacol. Therap.10, 298–304.

Dimethyl sulfoxide (DMSO) had been postulated to be a ‘masking agent’ when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfere with the detection of these drugs.
Serum levels and pharmacokinetics of ticarcillin and clavulanic acid in dog following parenteral administration of Timentin®
Authors: GARG R. C. , KEEFE T.J. , VIG M. M.
Published: April 2008

Garg, R.C., Keefe, T.J. & Vig, M.M. Serum levels and pharmacokinetics of ticarcillin and clavulanic acid in dog following parenteral administration of Timentin®. J. vet. Pharmacol. Therap. 10, 324–330.

The serum concentration‐time data for ticarcillin (TICAR) and clavulanic acid (CLA) following intravenous and intramuscular administration of Timentin® (TICAR, 50 mg/kg with CLA, 1.7 mg/kg) indicated that absorption of CLA following intramuscular injection and its overall elimination from the body was faster than that of TICAR. This is supported by comparison of certain pharmacokinetic parameters for TICAR and CLA. These include the shorter value of Tmax for CLA (11.45 ± 1.60 min) than that for TICAR (29.93 ± 1.94 min) and significant variation in the elimination rate constants (0.183 ± 0.0018 min‐1for CLA vs. 0.0097 ± 0.0006 min‐1for TICAR) for the intravenous group of animals. The biological half‐life of CLA (approximately 39 min) was significantly shorter (P < 0.01) than that of TICAR (approximately 73 min). In spite of initial faster absorption, the intramuscular bioavailability of CLA (65.02%) was less than that of TICAR (91.37%).

Though the pharmacokinetic behaviour of TICAR and CLA is not similar, yet based on the therapeutically optimal concentrations of CLA and TICAR reached in serum, Timentin®at the dose used in the present study should be effective in treating most TICAR‐resistant Enterobacteriaceae infections in dogs. Timentin®is not likely to be effective in the treatment of infections caused by TICAR‐resistant pseudomonads, at the dose used in the present study.
Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses
Authors: SHORT C. R. , BEADLE R. E. , ARANAS T. , PAWLUSIOW J. , CLARKE C. R.
Published: April 2008

The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two‐compartment open model. Cephapirin disappeared from serum rapidly (t½β= 18.8 min), and had only a modest volume of distribution (Kd(area) – 346 mg/kg, Vd(ss)– 204 ml/kg). Total clearance was also rapid (= 13 ml/min.kg). Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post‐injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment. The ratio of area under the curve (AUCo‐3 h) for serum : chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11:1. The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature. The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half‐life.
Pharmacotherapeutic aspects of medication of birds
Authors: DORRESTEIN G. M. , MIERT A. S.J. P. A. M. VAN
Published: April 2008

Dorrestein, G.M. & van Miert, A.S.J.P.A.M. Pharmacotherapeutic aspects of medication of birds. J. vet. Pharmacol. Therap. 11, 33–44.

This review covers current knowledge of the pharmacodynamics and pharmacokinetics of drugs in avian species. Special attention has been paid to inter‐species differences in relation to metabolic elimination, anatomy and physiology of the digestive and respiratory system, and differences in drug distribution. Intra‐species differences attributable to physicochemical aspects of the drug preparation and physiological conditions of the avian patient can also influence drug efficacy. The consequences of the choice of a particular method of drug administration on pharmacokinetics are also considered.
Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies
Authors: FIRTH E. C. , KLEIN W. R. , NOUWS J. F. M. , WENSING Th.
Published: April 2008

Firth, E.C., Klein, W.R., Nouws, J.F.M. & Wensing, Th. Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies. J. vet. Pharmacol. Therap. 11, 56–62.

Single doses of sodium ampicillin (10 mg/kg) and kanamycin sulfate (5 mg/kg) were administered intramuscularly (i.m.) separately, and then together, to five pony mares. The plasma antibiotic concentration–time curves were constructed. The pharmacokinetic parameters of the antibiotics given separately were not altered by concurrent administration. Four of the five pony mares were then given the i.m. kanamycin/ampicillin combination 4 h after acute synovitis and fever had been induced by injection of lipopolysaccharide into the left intercarpal joint. The plasma concentration–time curves and the synovial concentration–time curves of inflamed and normal joints were constructed. The Cmax of ampicillin in the lipopolysaccharide experiment was significantly higher than in the other experiments. The antibiotics entered the synovial fluid of the inflamed joints more quickly and attained higher concentrations than in the uninflamed joints. The ampicillin concentration exceeded 5 Jig/ml in inflamed synovial fluid for some 2.5 h after injection, and kanamycin sulfate concentration exceeded 2 μ.g/ml for 7 h.
Influence of inflammation on serum concentration, molecular heterogeneity and drug binding properties of canine alpha–1–acid glycoprotein
Authors: DELLO C. P. , BELPAIRE F. M. , RICK A. DE , FRAEYMAN N. H.
Published: April 2008

Dello, C.P., Belpaire, F.M., De Rick, A. & Fraeyman, N.H. Influence of inflammation of serum concentration, molecular heterogeneity and drug binding properties of canine alpha–1–acid glycoprotein. J. vet. Pharmacol. Therap.11, 71–76.

The concentration and the heterogeneity of alpha–1–acid glycoprotein (α–1–AGP) and oxprenolol binding were determined in serum of healthy dogs and dogs with inflammatory disease. In inflammation, an increase in the mean a–1–AGP concentration from 0.47 to 2.85 g/1 was accompanied by a reduction in the mean free oxprenolol fraction from 25% to 6%. α–l–AGP concentration and oxprenolol binding were inversely correlated. The heterogeneity of canine a–l–AGP remained essentially unchanged in dogs with inflammation and, in both these dogs and the controls, between five and seven forms with different isoelectric points and one single concanavalin A–reactive form were detected. It is concluded that in dogs, as in humans, oxprenolol binds to serum α–l–AGP. Changes in serum binding of oxprenolol during inflammation result from a change in the serum concentration of a–l–AGP rather than a change of molecular heterogeneity.
The correlation of the thermal and mechanical antinociceptive activity of pethidine hydrochloride with plasma concentrations of the drug in sheep
Authors: NOLAN A. , WATERMAN A. E. , LIVINGSTON A.
Published: April 2008

Nolan, A., Waterman, A.E., Livingston, A. The correlation of the thermal and mechanical antinociceptive activity of pethidine hydrochloride with plasma concentrations of the drug in sheep. J. vet. Pharmacol. Therap. 11, 94–102.

The analgesic activity of pethidine was measured in eight sheep using both thermal and mechanical test systems. Pethidine, at a dose rate of 5 mg/kg body weight given intravenously, produced a significant degree of antinociception to thermal pain for 30 min (on average) but gave only a few minutes of significant analgesia when tested in the mechanical pressure system. Analgesia in both systems was abolished by pretreatment with naloxone. Pharmacokinetic analyses of plasma levels of pethidine after intravenous (i.v.) injection were carried out. Plasma concentrations of the drug exhibited a rapid biexponential pattern of decline with an average distribution half‐life of 0.99 min and an elimination half‐life of 12.8 min. Correlation of plasma levels of the drug with the presence of a significant degree of antinociception in the thermal test system enabled ‘critical’ analgesic levels of pethidine to be defined for sheep (0.93 μg/ml).
Effect of diuretics on ketamine and sulfanilate elimination in cats
Authors: HANNA R. M. , BORCHARD R. E. , SCHMIDT S. L.
Published: April 2008

Hanna, R.M. Borchard, R.E. & Schmidt, S.L. Effect of diuretics on ketamine and sulfanilate elimination in cats. J. vet. Pharmacol. Therap. 11, 121–129.

Rate constants of elimination were used to evaluate potential effects of diuretic agents on the elimination of ketamine from the blood of cats. Furosemide, mannitol, and aminophylline did not significantly alter the ketamine elimination rate constants, although the diuretics had a tendency to prolong elimination. This tendency of furosemide was further substantiated by observing the effect of furosemide on glomerular filtration. The rate of sulfanilate elimination, used as an indicator of glomerular filtration, was significantly decreased in the cats that were administered furosemide. Possible mechanisms for the influence of furosemide on the renal excretion of ketamine are discussed.
The effect of testosterone and rutting on the metabolism and pharmacokinetics of sulphadimidine in goats
Authors: NOUWS J. F. M. , MEESEN B. P. W. , GOGH H. VAN , KORSTANJE C. , MIERT A. S.J. P. A. M. VAN , VREE T. B. , DEGEN M.
Published: April 2008

Nouws, J.F.M., Meesen, B.P.W., Gogh, H. van, Korstanje, C., Miert, A.S.J.P.A.M., Vree, T.B. & Degen, M. The effect of testosterone and rutting on the metabolism and pharmacokinetics of sulphadimidine in goats. J. vet. Pharmacol. Therap.11, 145–154.

After testosterone pretreatment of castrated goats and during the rutting season of adult entire male goats, the oxidative metabolism of sulphadimidine (SDM) was inhibited markedly compared with the castrated control state of these animals. The oxidation of the 5 position (yielding 5‐hydroxysulphadimidine) and of the 6‐hydroxymethyl group (yielding 6‐carboxysulphadimidine) was decreased equally, with that of the methyl group at the pyrimidine side chain itself being 6‐hydroxymethylsulphadimidine (CH2OH), whereas the acetylation pathway was unaffected by testosterone. The consequence of altered metabolism by testosterone was a prolongation of SDM presence in the body. Effects on protein binding of the CH2OH metabolite and on the renal clearance of SDM were also investigated.
Letter to the Editors
Authors: GIBB MICHAEL
Published: April 2008

DISEASES OF THE THORAX – RADIOGRAPHIC DIAGNOSIS. Peter F. Suter, Juan A. Gomez

RADIOLOGY OF SKELETAL DISEASE – PRINCIPLES OF DIAGNOSIS IN THE DOG. J. P. Morgan
Pharmacokinetics and efficacy of triclabendazole in goats with induced fascioliasis
Authors: KINAB L. D. B. , BOGAN THE LATE‘ J. A.
Published: April 2008

Kinabo, L.D.B. & Bogan, J.A. (deceased). Pharmacokinetics and efficacy of triclabendazole in goats with induced fascioliasis. J. vet. Pharmacol. Therap.11, 254–259.

The pharmacokinetics of triclabendazole were evaluated in normal goats and in goats artificially infected with Fasciola hepatica. Triclabendazole and its metabolites were determined using a novel high performance liquid chromatographic method with fluorimetric detection after solid‐phase extraction. In normal goats triclabendazole given orally was metabolized rapidly to its sulphoxide and sulphone derivatives. The maximum plasma concentrations for the sulphoxide and sulphone were similar ranging from 9 to 19 Hg/ml and these were attained at an average 12.8 and 25.6 h, respectively, after administration. Both metabolites were eliminated slowly from plasma with elimination half‐lives of 22.4 h for the sulphoxide and 19.4 h for the sulphone. They persisted at measurable concentrations in plasma for up to seven days. In milk, the two metabolites occurred in low concentrations and none of them was detectable (sulphoxide < 0.04 Hg/ml, sulphone < 0.02 (xg/ml) after seven days. The pharmacokinetic behaviour of triclabendazole was not altered in animals with fascioliasis. Efficacy of the drug against immature (six‐week) F. hepatica was 100%.
Salmonella colonization in young chickens given feed supplemented with the growth promoting antibiotic avilamycin
Authors: HINTON M.
Published: April 2008

Hinton, M. Salmonella colonization in young chickens given feed supplemented with the growth promoting antibiotic avilamycin. J. vet. Pharmacol. Therap. 11, 269–275, 1988.

The feed given to young broiler chickens was contaminated artificially with Salmonella kedougou, a serotype associated with both subclinical infections in commercially reared chickens and food poisoning in humans. No evidence was obtained to suggest that the growth promoting antibiotic avilamycin, added to the feed at the rate of either 2.5 ppm or 10 ppm, had the undesirable side‐effect of favouring the colonization of the intestinal tract of the birds with Salmonella kedougou when they were challenged with this organism in the feed.
Inhibition of rumination in sheep by α‐adrenoreceptor antagonists
Authors: NICHOLSON T. , OSMAN T. E. A. , BELKHIRI M.
Published: April 2008

Nicholson, T., Osman, T.E.A. & Belkhiri, M. Inhibition of rumination in sheep by α‐adrenoreceptor antagonists.J, vet. Pharmacol. Therap. 11, 276–282, 1988.

Rumination activity was recorded in sheep during a period of 3 h. The amount of rumination occurring in 30 min following the intravenous injection of an α blocking drug (prazosin, 0.1 mg/kg) and an a2 blocking drug (idazoxan, 0.1 mg/kg) was reduced compared with control days when saline was given. The observation that rumination can be stimulated by a rapid, intravenous dose of adrenalin was confirmed. The induction of rumination by adrenalin was prevented by these α ‐adrenoreceptor antagonists given singly or together at the dose rate mentioned. These findings are discussed in the light of knowledge that normal reticulo‐ruminal motility and food intake can be inhibited by stimulation of α ‐adrenoreceptors.
Parainfluenza‐3 virus‐induced enhancement of histamine release from calf lung mast cells – effect of levamisole
Authors: OGUNBIYI P. O. , BLACK W. D. , EYRE P.
Published: April 2008

Ogunbiyi, P.O., Black, W.D. & Eyre, P. Parainfluenza‐3 virus‐induced enhancement of histamine release from calf lung mast cells – effect of levamisole.J. vet. Pharmacol. Therap.11, 338–344.

Clinically healthy calves were divided into five groups. Group 1 served as control; Group 2 received levamisole (LEV), 3 mg/kg, s.c; Group 3 was aerosolized with parainfluenza‐3 virus (PI‐3); Group 4 received LEV and PI‐3 and Group 5 was inoculated with Pasteurella haemolytica. They were killed 6 days after virus exposure or 5–6 days after bacterial inoculation. Lung mast cells were prepared by enzymatic treatment. Mast cell histamine (HIST) release was assayed spectro‐fluorometrically. Total HIST (m̈g/g) in mast cells was as follows (x̄± SEM): control (5.30 ± 0.26); LEV (5.27 ± 0.31); PI‐3 (6.37 ± 0.65); LEV ± Pl‐3 (6.21 ± 0.51); P. haemolytica (7.06 ± 0.85). Spontaneous HIST release was as follows (% total, x̄± SEM): control (10.38 ± 1.09), LEV (11.95 ± 2.13), PI‐3v (73.57 ± 11.97), PI‐3v ± LEV (19.50 ± 3.03), and P. haemolytica (70.59 ± 5.94). Calcium ionophore A23187 (5 times 10‐6 M) ‐induced release (% total, x̄± SEM) was: 51.53 ± 3.05, 50.02 ± 2.70, 83.91 ± 4.09, 75.21 ± 4.51 and 70.59 ± 6.91 for control, LEV, PI‐3, LEV ± PI‐3 and P. haemolytica groups, respectively. Both virus and bacteria increased HIST content of lung mast cells and enhanced ionophore‐induced release. Levamisole significantly reduced spontaneous HIST release in virus‐infected calves but had no effect on ionophore‐induced release. Results suggest a significant role for HIST in pathogenesis of bovine microbial pneumonia and that LEV probably does not modulate non‐immunologic release of HIST from bovine lungs.
Comparative effects of etomidate and its fluoro analogue, R 8110 on testicular, adrenal and ovarian steroid biosynthesis
Authors: COSTER R. DE , WOUTERS W. , BEERENS D. , HAELTERMAN C. , DOOLAEGE R. , GOEMINNE N. , KREKELS M.
Published: April 2008

De Coster, R., Wouters, W., Beerens, D., Haelterman, C, Doolaege, R., Goeminne, N. & Krekels, M. Comparative effects of etomidate and its fluoro analogue, R 8110 on testicular, adrenal and ovarian steroid biosynthesis. J. vet. Pharmacol. Therap.11, 345–353.

The effects, of etomidate and of its fluoro analogue, R 8110, on adrenal, testicular and ovarian steroid biosynthesis were compared using cultures of guinea‐pig adrenal, rat adrenal capsular, rat testicular and rat ovarian granulosa cells. At a concentration of 100 nM, etomidate inhibited the adrenal 11‐hydroxylation of glucocorticoid and mineralocorticoid biosyntheses, producing a decrease in Cortisol and corticosterone and an accumulation of 11‐deoxycortisol and 11‐deoxycorticosterone in guinea‐pig adrenal and rat capsular adrenal cell suspensions, respectively. At higher concentrations (> 10‐6 M), etomidate also inhibited ovarian oestradiol production, testicular androgen formation and ovarian progesterone synthesis. The latter action suggests an effect on ovarian aroma‐tase, on testicular 17a/17,20‐lyase activities and Finally on cholesterol side‐chain cleavage. The fluoro analogue of etomidate, R 8110, was ten times less potent as an inhibitor of 11‐hydroxylation and affected progesterone formation only slightly in adrenal cell suspensions. Testosterone production was less affected by R 8110 than by etomidate. The increase of progestins suggests that the 17a/ 17,20‐lyase activities are the most sensitive testicular enzymatic reactions to R 8110. For inhibition of ovarian oestradiol production, R 8110 was twenty times more potent than etomidate.
Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2‐receptor antagonist
Authors: ZAVY M. T. , LINDSEY T. O. , HEDDE R. D.
Published: April 2008

Zavy, M.T., Lindsey, T.O. & Hedde, R.D. Gizzard ulceration in chicks fed cysteamine alone or in combination with a histamine H2‐receptor antagonist. J. vet. Pharmacol. Therap. 11, 362–373.

A study was carried out to evaluate the effect of cysteamine‐HCl administration on gizzard ulceration and growth performance in broiler chicks. The effectiveness of the histamine H2‐receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine‐HCl was also examined. In the initial experiment cysteamine‐HCl at the level of 2400 mg/kg of the diet caused severe gizzard ulceration and mortality and decreased feed intake and growth in chicks. The effect was not seen when cysteamine‐HCl was administered at 600 or 1200 mg/kg of the diet. In Experiment 2 broiler chicks administered cysteamine‐HCl at 1800 mg/kg of the diet had an increased incidence of gizzard ulceration and decreased growth performance. The severity of gizzard lesions and the depression of growth performance were not as great as in the group in Experiment 1 which received the 2400 mg/kg level of cysteamine‐HCl. Addition of the H2 antagonist SKF 93479 at 54 mg/kg of the diet had no effect on improving gizzard ulcer score or growth performance in chicks which received cysteamine‐HCl at the 1800 mg/kg of the diet level. From these data it appears that the administration of ulcerogenic levels of cysteamine‐HCl in the chicken may involve a more complex pathogenesis in which factors other than acid hypersecretion are involved.
Determination of the acute oral toxicity of theophylline in conscious dogs
Authors: MUNSIFF I.J. , MCKIERNAN B.C. , NEFF‐DAVIS C. A. , KORITZ G. D.
Published: April 2008

Munsiff, I.J., McKiernan, B.C., Neff‐Davis, C.A. & Koritz, CD. Determination of the acute oral toxicity of theophylline in conscious dogs. J. vet. Pharmacol. Therap. 11, 381–389.

The purpose of this study was to define the minimum toxic concentrations and clinical signs of theophylline toxicity in healthy, conscious dogs. Five dogs were dosed orally in a five‐way crossover design with sustained release theophylline (Theo‐Dur® tablets, Key Pharmaceuticals) at 0, 20, 40, 80, and 160 mg/kg. They were observed for a 9‐h period for clinical signs of toxicity which had been previously determined in a pilot study. These signs included sinus tachycardia and central nervous stimulation (manifested as restlessness, excitement, or vomition). The Physiotel® radiotransmitter telemetry system was used for the acquisition of the heart rate and ECG. Blood samples were obtained every hour for theophylline determination by high pressure liquid chromatography. The results showed that toxicity occurs at higher theophylline plasma concentrations in the dog (37–60 m̈g/ml) as compared to man (> 20 m̈g/ml) when dosed orally. Since current dosage regimens in dogs are designed to maintain trough‐peak theophylline plasma concentrations between 10 and 20 m̈g/ml, the results indicate that the upper limit of this range appears to be safe in the dog.
Sustained‐release theophylline pharmacokinetics in the cat
Authors: DYE J. A. , McKIERNAN B. C. , D.JONES S. , NEFF‐DAVIS C. A. , KORITZ G. D.
Published: April 2008

Theophylline was administered in a three‐way crossover design study to six cats intravenously (Aminophylline USP, Invenex Laboratories, Chagrin Falls, OH) and orally as two sustained‐release formulations (Slo‐bid Gyrocaps® (SB), William H. Rorer, Inc., Fort Washington, PA; Theo‐Dur® Tablets (TD), Key Pharmaceuticals, Miami, FL). Values were determined for mean residence time (SB = 19.4 ± 3.2 h; TD = 15.8 ± 4.8 h), mean absorption time (SB = 8.0 ± 2.3 h; TD = 4.8 ± 2.3 h), absolute bioavailability (SB = 82 ± 27%; TD = 76 ± 38%), and time to peak plasma concentrations (SB = 8 h; TD = 8 h). After normalization to a dose of 25 mg/kg, the average peak plasma concentrations were also predicted (SB = 10.5 ± 3.4 μg/ml; TD = 14.3 ± 6.7 μg/ml). Slo‐bid® was predicted to provide the least peak: trough fluctuation in theophylline concentrations. Slo‐bid® and Theo‐Dur® appear to have pharmacokinetic characteristics which, if given once‐daily, would maintain plasma theophylline concentrations of 5–20 μg/ml in the cat.
Intra‐abdominal versus intramuscular application of two ampicillin preparations in cows
Authors: KLEIN W. R. , FIRTH E. C. , KIEVITS J. M. C. A. , JAGER J. C. DE
Published: April 2008

Plasma ampicillin concentrations were determined in a cross‐over trial involving five cows after single intramuscular or intra‐abdominal administration of sodium ampicillin (10 mg/kg) and ampicillin anhydrate (40 mg/kg). After injection of sodium‐ampicillin, high plasma concentrations were reached within 10 min; Cmax following intramuscular injection was 9.1 μg/ml and after intraabdominal injection 7.5 μg/ml. Urine concentrations of ampicillin were low after 24 h (1–1.5 μg/ml). No significant changes in blood leucocyte numbers, plasma zinc, iron or fibrinogen levels occurred. After injection of ampicillin anhydrate 1 h elapsed before maximum plasma levels were obtained; Cmax was 5.4 μg/ml after intramuscular and 6.7 μg/ml after intra‐abdominal administration. Urine concentrations were very high (238–303 μg/ml) after 24 h and stayed above 1 (μg/ml for 6 days. After administration of ampicillin anhydrate a significant increase in blood neutrophils (P < 0.01) and a significant increase in plasma fibrinogen was measured after intramuscular and intra‐abdominal injection (P < 0.05). A significant decrease in plasma zinc concentration after intra‐abdominal injection occurred (P < 0.05). In abdominal surgery in cows in which contamination cannot be prevented, and practical objections inhibit preoperative administration, intramuscular or intra‐abdominal administration during surgery of sodium ampicillin seems justified. Ampicillin anhydrate should not be used intra‐abdominally.
Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST, zeranol and proligestone
Authors: WITKAMP R. F. , NIJMEIJER S. M. , DUIN C. T. M. VAN , BEVERS M. M. , WENSING TH. , GOGH H. VAN , MIERT A.S.J.P.A.M. VAN
Published: April 2008

Daily subcutaneous BST injection in lactating cows, bulls and castrated male dwarf goats did not induce significant changes in the pharmacokinetic parameters of antipyrine (AP) and sulphadimidine (SDD). Similarly, no changes were obtained after injection of slow‐release BST formulations in lactating cows and non‐lactating female goats. In contrast to androgenic hormones, both zeranol and proligestone had no effect upon the disposition of AP and SDD, although both synthetic hormones did induce enhanced plasma somatotropin concentrations. In goats, metabolic effects induced by zeranol and BST included significant reductions in plasma urea values, whereas plasma creatinine levels were somewhat lower after daily BST administration.
Pharmacokinetics and cardio‐respiratory effects of oral theophylline in exercised horses
Authors: INGVAST‐LARSSON C. , KALLINGS P. , PERSSON. S. , APPELGREN L.‐E. , WIESE B.
Published: April 2008

The pharmacokinetics of theophylline at rest and the effects on cardiorespiratory and blood lactate responses to exercise were investigated after repeated oral administrations in six healthy Standardbred horses. A dose of 5 mg/kg body weight was administered every 12 h. The binding of theophylline to plasma protein was also determined. There was good agreement between predicted and observed plasma concentrations of theophylline at steady state. The mean half‐life of elimination was shown to be 17.0 ± 2.5 h, the mean half life of absorption was 1.6 ± 1.8 h, the apparant volume of distribution was 852 ± 99.0 ml/kg and total plasma clearance 0.61 ± 0.08 ml/kg/min. Theophylline showed very low plasma protein binding (12%). The heart rate and blood lactate levels, during and after exercise, were significantly increased during theophylline‐treatment. There was an increase of the arterial oxygen tension after exercise and the arterial carbon dioxide values before and after exercise were significantly lower than the premedication values. No severe adverse effects of the drug were noted. The recommended oral dose is therefore 5 mg/kg every 12 h but due to inter‐individual variation, an adjustment of the dose may be necessary. The changes in the studied exercise parameters indicate that the performance capacity may be impaired by theophylline in the healthy horse.
Effects of fenbendazole administration on hematology, clinical chemistries and selected hormones in the white Pekin duck
Authors: PEDERSOLI W. M. , SPANO J. S. , KRISTA. L. M. , WHITESIDES. J. F. , RAVISH W. R. , KEMPPAINEN R.J. , YOUNG D. W.
Published: April 2008

The effects of single i.v. and p.o. doses (5 mg/kg) of fenbendazole were evaluated on thyroxine, tri‐iodothyronine, corticosterone, hematology, clinical chemistries, and serum proteins in 10 white Pekin ducks. Fenbendazole was administered i.v. (n= 5) as a 3% dimethyl sulfoxide solution and p.o. (n= 5) as a 10% commercial suspension. Serum enzyme concentrations, total protein and protein fractions, glucose, cholesterol, uric acid, sodium, and potassium were unchanged from baseline values. Serum triglycerides decreased consistently in the i.v.‐treated group but remained unchanged in the p.o.‐treated group. Serum chloride was consistently elevated above baseline values for both i.v.‐ and p.o.‐treated ducks, while inorganic phosphate was consistently decreased only in the i.v.‐treated group. Hemoglobin and hematocrit values generally were below baseline values. Leukocyte values varied considerably and were not significantly different from baseline values. Serum thyroxine and tri‐iodothyronine values in both the i.v.‐ and p.o.‐treated groups were not changed significantly from baseline values. Serum corticosterone values were not changed in the i.v.‐treated groups but they were decreased at various times in the p.o.‐treated group. Although there were some sporadic significant changes in the parameters measured versus baseline values all values remained within the physiologic limits for ducks. The safety of fenbendazole has been previously demonstrated for several species.
Sedative and analgesic effects of medetomidine in dogs
Authors: VAINIO O. , VÄHA‐VÄHE T. , PALMU L.
Published: April 2008

Vainio, O., Vähä‐Vahe, T. & Palmu, L. Sedative and analgesic effects of medetomidine in dogs. J. vet. Pharmacol. Therap.12, 225–231.

The sedative and analgesic effects of medetomidine were studied in 18 laboratory beagles in a randomized cross‐over study which was carried out in a double‐blind fashion. Xylazine was included as a positive control and placebo as a negative control. Medetomidine was used at doses of 10, 30, 90 and 180 μg/kg i.m. compared to a dose of 2.2 mg/kg xylazine i.m. Parameters closely related to sedation were used to measure the degree of sedation. These were a posture variable (including evaluation of the dog's posture without external disturbance and resistance when laid recumbent) and a relaxation variable (including relaxation of the jaws, upper eyelids and anal sphincter). The First signs of sedation were recorded 1.5–3.5 min after administration of both drugs. The dogs sat down at 0.6–2.6 min post‐injection and became prone at 1.9‐5.9 min. Medetomidine dose‐dependently affected the posture of the dogs and the relaxation variable — the higher the dose, the stronger and longer lasting the effect recorded. The sedative effect of xylazine was comparable to a medetomidine dose of 30 μg/kg. The analgesic effect was assessed as changes in the response to superficial pain induced by electrical stimuli. The response threshold increased significantly with both drugs and the effect of medetomidine was dose‐dependent. The effects of the doses of 30 μg/kg medetomidine and 2.2 mg/kg xylazine did not differ significantly. In summary, medetomidine possessed an excellent sedative effect associated with analgesia in dogs.
Wasting pig syndrome (WPS) in weaners — treatment with amperozide
Authors: KYRIAKIS S. C. , ANDERSSON G.
Published: April 2008

Social and environmental stressors during the critical period of weaning frequently affect not only performance but also the health status of piglets. Pigs unable to cope with the changes associated with weaning develop a condition characterized by slowing of growth and a listless or unthrifty appearance, known as the wasting pig syndrome (WPS). In the present investigation a total of 100 4‐week‐oId wasting pigs were studied. The pigs were divided randomly into 10 pens (10 animals per pen). Half the number of pigs were treated orally with amperozide (2.5 mg/kg body‐weight), a psychotropic drug shown to modify emotional behaviour in response to social stress. Control groups were treated with long‐acting oxytetracycline and vitamins (A+D3+E). There were significant improvements in average daily weight gain (P < 0.05) and feed conversion ratio (P < 0.01) in amperozide‐treated pigs compared with controls. Furthermore, there was a significant reduction (P < 0.05) in mortality in amperozide treated groups. Within 2 weeks following amperozide treatment the clinical signs of the WPS had disappeared and the pigs grew at the same rate as normal healthy pigs.
Doxycycline binding to plasma albumin of several species
Authors: RIOND J.‐L. , RIVIERE J. E.
Published: April 2008

The affinity of doxycycline for crystalline plasma albumin fraction V, originating from sheep, dogs, cats, cows, pigs and humans, was evaluated by means of double‐reciprocal and Scatchard plots. Mathematical modelling and weighted least‐squares non‐linear regression analysis of each Scatchard plot identified one binding component characterized by one high affinity binding site, and a second component attributed to non‐specific binding to albumin. Association constants for this binding site ranged from 38 471 ± 13 369 (SEM) l/mol for the interaction of doxycycline with ovine albumin to 6405 ± 2375 l/mol for the interaction of doxycycline with human albumin. Statistical evaluation of the results suggested slight species‐related differences in the values of association constants. Diphenylhydantoin, phenobarbital or carbamazepine did not displace doxycycline from binding sites on bovine albumin.