bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of anticholinergic drugs on the electrical activity of the antrum and duodeno‐jejunum in sheep
Authors: BUENO L. , RUCKEBUSCH Y.
Published: April 2008

The changes induced in the electrical activity of the small intestine by atropine sulphate, diphemanil methylsulphate, hyoscine butylbromide and prifinium bromide were studied in conscious sheep fitted with chronically implanted electrodes. Increased spike potential activity was induced by carbachol. The mean slow‐wave frequency of the antrum was 7.35 ± 0.18/min with burst of spike potentials randomly superimposed on about 63% of the slow waves. The occurrence of the spike bursts was inhibited for 18—30 min after an intravenous injection of atropine (0.75 mg/kg) and during its infusion at the rate of 0.05 mg/kg/min. The activity of the proximal part of the small intestine, which is characterized by migrating myoelectric complexes moving down slowly at hourly intervals, was replaced by irregular series consisting of spike bursts of about 3 min duration, at intervals of about 12 min for a total of 110 min. Such an effect, in which the level of spike activity was reduced, was also observed with hyoscine, diphemanil and prifinium during 80, 120 and 180 min periods respectively. The injection of carbachol was followed by continuous spike activity in which the mean spike level was nearly doubled, as occurs at the onset of diarrhoea. An inhibitory effect was observed at both antral and duodeno‐jejunal levels with the four drugs used, that of hyoscine being least marked. The effect of prifinium was more pronounced than that of atropine or diphemanil, especially on the jejunum. The results suggest that the ability of these drugs to reduce the level of spike activity accompanying disruption of migrating myoelectric complexes and to inhibit the carbachol‐induced increased level of spiking may account for the antispasmodic effects observed after the use of anticholinergic drugs in gastrointestinal disorders. Prifinium had the longest lasting effect at both antral and duodeno‐jejunal levels and seemed to be a good atropine substitute to alleviate gastro‐intestinal hypermotility.
Methylene blue or tolonium chloride antagonism of sodium nitrite induced methemoglobinemia
Authors: BURROWS G.E.
Published: April 2008

Methylene blue is widely accepted as an antidote for nitrite toxicosis because of its ability to stimulate reduction of methemoglobin (ferrihemoglobin) to hemoglobin. It is usually used only in low dosage (4mg/kg) because of its purported enhancement of methemoglobin formation in high dosages. Methylene blue was evaluated as a nitrite toxicosis antidote using methemoglobin reduction and lethality protection as evaluation parameters. Tolonium chloride (toluidine blue) another structurally related dye was also evaluated using the same parameters. Both dyes were very effective antidotes. Methylene blue increased in effectiveness as the dose was increased up to 22 mg/kg. Tolonium chloride provided approximately equivalent protection at 8.8 mg/kg but may be more toxic than methylene blue. High concentrations of either dye did not result in appreciable production of methemoglobin. In cases of severe intoxication by methemoglobin formers such as nitrite, larger doses of methylene blue than generally recommended, may be of considerable therapeutic value.
Pharmacokinetic interaction of isopropylaminophenazone and phenylbutazone in the horse
Authors: JENNY EDUARD , STEINIJANS VOLKER W. , SEIFERT PHILIPPE
Published: April 2008

The pharmacokinetics of the two active anti‐inflammatory compounds, isopropylaminophenazone and phenylbutazone, were investigated in the horse. Therapeutic intravenous doses of 12 mg/kg body weight and 6 mg/kg body weight, respectively, were given separately and as a combination to five horses. Blood concentrations were described by two‐compartment kinetics. Significantly lower total clearances, unchanged volumes of distribution, and hence significantly higher elimination half‐lives were found for both substances when administered as a combination. It is possible that the hydroxylated metabolites of the substances are responsible for the presumed metabolic interference.
Pharmacokinetics of antipyrine and trimethoprim in pigs with endotoxin‐induced fever
Authors: LADEFOGED OLE
Published: April 2008

Oral administration of antipyrine or trimethoprim to normal and endotoxin‐pretreated, febrile pigs resulted in pharmacokinetic parameters which were different in the two groups of pigs. The one‐compartment model with first order absorption rate constant can be used to describe the pharmacokinetics of antipyrine and trimethoprim in normal pigs but cannot satisfactorily describe the plasma concentration versus time data in the febrile pigs. The absorption rate and the elimination rate of antipyrine and trimethoprim are reduced in the febrile pigs whereas the volume of distribution is increased.
Pharmacokinetics of nine sulphonamides in goats
Authors: GOGH HENK VAN
Published: April 2008

Pharmacokinetics of nine sulphonamides was investigated in healthy goats. From the plasma disappearance curves after intravenous bolus injection clearance rates, plasma half‐lives and distribution volumes were calculated. Plasma‐protein binding was measured in vitro and in vivo. The highest‐bound sulphonamides showed the highest concentration dependence of protein binding.

Plasma disappearance curves were in accordance with the one‐, two‐ or three‐compartment pharmacokinetic models. Disposition of sulphadimidine after 100 or 200 mg/kg and of sulphisomidine after 200 mg/kg showed limited enzyme capacity characteristics. Disposition of sulphadimidine, sulphisomidine and sulphadimethoxine was dose‐dependent. Goats could also be divided in fast and slow sulphadimidine eliminators. Correlation was found only between clearance and half‐life. Dosage regimens were calculated for seven sulphonamides.
Pharmacokinetics of chloramphenicol in calves during the first weeks of life
Authors: REICHE R. , MÜLLING M. , FREY H.‐H.
Published: April 2008

The pharmacokinetics of chloramphenicol, either administered as the monosuccinate ester or as a veterinary formulation, were studied in calves from the first day of life to the age of 10–12 weeks and compared with the results obtained in adult cattle.

(1) After intravenous injection of 0.15 mmol/kg chloramphenicol monosuccinate, the plasma elimination half life of intact ester fell from a value of 33 min on the first day of life to 15 min at the age of 10–12 weeks (value in cows = 14 min). Free chloramphenicol reached maximal plasma concentrations after 2–3 h on the first day of life, but in less than 15 min in cows. The elimination half‐life fell from about 15 h on day 1 to 4.8 h at the age of 10–12 weeks (4.2 h in cows). The bioavailability of the ester was more than 90% on Day 1, but declined to 50–60% from Day 7 on account of rapid renal excretion: 21–28% of the total dose was excreted as intact ester in a 2 h period following injection in calves aged 10–12 weeks.

(2) The veterinary formulation of chloramphenicol proved toxic when administered intravenously at a dose of 0.15 mmol/kg, and even a dose of 0.093 mmol/kg was less well tolerated than 0.15 mmol/kg of the monosuccinate ester.

(3) The pharmacokinetics of chloramphenicol fitted an open two‐compartment model, the half‐life of the elimination phase corresponded well to the values determined in the experiments with the monosuccinate ester.

(4) The intramuscular injection of 0.15 mmol/kg of the ester or 0.093 mmol/kg of chloramphenicol provided ‘therapeutic’ plasma concentrations (≥ 5 μg/ml) within 15–30 min and for about 24 h in calves aged 7 days.

(5) Chloramphenicol crossed the placenta when given to cows shortly before a Caesarian section, but equilibrium was not reached within 50–100 min.

(6) The binding of chloramphenicol to serum proteins was dependent both on total protein and drug concentrations. It rose from less than 30% on day 1 to about 40% in adult cattle.

(7) Recommendations for a dosage regime for chloramphenicol in calves are made on the basis of the pharmacokinetic data.
Some physiological and biochemical effects of intravenous fluid administration during halothane anaesthesia in the dog
Authors: ROSE R. J. , CARTER R. J. , ILKIW JAN E.
Published: April 2008

Six dogs with previously implanted arterial, central venous, pulmonary arterial and left atrial catheters received halothane anaesthesia, and halothane anaesthesia plus administration of a balanced electrolyte solution given over one hour, in a cross‐over experiment. Parameters measured included temperature, heart rate (HR), respiratory rate (f), arterial and mixed venous blood‐gases and acid‐base parameters, mean arterial pressure (AP), mean pulmonary artery pressure (PAP), mean left atrial pressure (LAP), mean central venous pressure (CVP), packed cell volume (PCV), total plasma protein (TPP), plasma sodium, potassium and chloride concentrations, and urinary sodium and potassium concentrations.

During halothane anaesthesia there were significant decreases in AP, PCV, TPP, f, and significant increases in arterial and mixed venous oxygen, and glucose concentrations, when compared with conscious control values. When intravenous fluid was administered during anaesthesia, there were significant decreases in temperature, AP, PCV and TPP, with significant increases in PAP, CVP and f, when compared with values during anaesthesia alone. After one hour recovery period from anaesthesia, dogs receiving intravenous fluids had significantly decreased PaO2 values and significantly increased pH when compared with anaesthesia alone. There was an average urinary excretion of 7 mmol of sodium and 5 mmol of potassium during anaesthesia, and 36 mmol of sodium and 8 mmol potassium during fluid administration.
Bioavailability and pharmacokinetics of phenylbutazone in the cow
Authors: DE BACKER P. , BRAECKMAN R. , BELPAIRE F. , DEBACKERE M.
Published: April 2008

Phenylbutazone was administered orally and intravenously at a dose of 5 mg/kg to healthy cows and to cows positive for bovine leukaemia virus (BLV). Pharmacokinetic parameters and bioavailability were investigated. No differences were seen in the parameters between the healthy and BLV positive animals. The biological half‐lives ranged from 31.4 to 82.1 h after intravenous administration and from 38.6 to 78.2 h after oral administration. The mean value of the apparent volume of distribution was 0.09 litres/kg. Total body clearance ranged from 0.78 to 1.94 ml/kg/h. The average systemic availability was 67.5% with a wide variation among the animals (range 41.9–95.5%). Based on the disposition kinetics and on the therapeutic concentration range suggested in man, an oral loading dose ranging from 10 to 20 mg/kg and a daily maintenance dose ranging from 2.5 to 5 mg/kg can be proposed.
The effect of pre‐treatment with phenylbutazone or soy‐bean trypsin inhibitor on experimental equine E. coli endotoxemia
Authors: BURROWS GEORGE E.
Published: April 2008

The investigation was supported by the National Institutes of Health, General Research Support Grant FR 5465 Administered through the College of Veterinary Medicine, Washington State University.
Bioavailability of oxytetracycline dihydrate tablets in dogs
Authors: COOKE R. G. , KNIFTON A. , MURDOCH D. B. , YACOUB I. S.
Published: April 2008

Plasma oxytetracycline concentrations were studied in four healthy beagles after oral administration of four different commercial preparations of oxytetracycline dihydrate tablets. Although no statistically significant differences were found in the biological availability between the four tablets, assessed by the peak plasma level and the area under the plasma concentration—time curve, there was great variation in the plasma concentrations of oxytetracycline achieved in the sixteen experiments. This variation was not related to the in vitro dissolution properties of the tablets. As the amount of oxytetracycline dihydrate administered in die experiments was almost the maximum recommended dose and the mean peak plasma concentrations were either below or at the lower end of the therapeutic concentration range, it is suggested that higher oral doses than those officially recommended are required to attain effective plasma levels.
The susceptibility of isolates of Corynebacterium equi to antimicrobial drugs
Authors: PRESCOTT J. F.
Published: April 2008

Fifty‐one isolates of Corynebacterium equi recovered from pigs and horses belonging to two capsular serotypes were tested for susceptibility to antimicrobial agents. No clear differences were detected in sensitivity between isolates of different sources or serotypes. All isolates were sensitive to <0.25 μg/ml of erythromycin and gentamicin. The following minimum inhibitory concentrations (MICs) of antimicrobial agents were determined for ≤90% of isolates: methicillin >16 μg/ml, clindamycin 1–2 μg/ml, tobramycin ≤1 μg/ml, cephalothin 8–64 μg/ml, kanamycin 2–8 μg/ml, amikacin ≤1–2 μg/ml, penicillin 2–≤4 μg/ml, ampicillin 2–8 μg/ml, trimethoprim‐sulfa 4/76–32/608 μg/ml tetracycline 1–4 μg/ml and chloramphenicol 8–16 μg/ml.
A study of fluctuations in Escherichia coli sensitivity patterns from pigs fed a halquinol supplemented diet
Authors: COSGROVE R. F. , FORSTER T. C. , JONES G. T. , PICKLES R. W.
Published: April 2008

Escherichia coli isolated from pigs fed on a medicated diet containing 120 p.p.m. halquinol did not develop any resistance to this addition over a 6‐week period.

Sensitivity patterns of the E. coli isolates to eight antimicrobial substances, although fluctuating slightly during the test period (but no more than a control group), did not significantly alter. However, the patterns did change significantly when for 17 days after the completion of the halquinol trial the pigs were fed a normal commercial ration medicated with a commonly used feed additive containing chlortetracycline hydrochloride, procaine penicillin and sulphadimidine.
Cardiopulmonary effects of clenbuterol in the horse
Authors: SHAPLAND JAMES E. , GARNER HAROLD E. , HATFIELD DAN G.
Published: April 2008

Clenbuterol, a bronchospasmolytic agent (β2 agonist) was studied in terms of its hemodynamic and airflow response in eight, healthy horses. Four animals were instrumented to record intrapleural pressure and air flow, these were used to compute pulmonary resistance, peak flow rates, and tidal volumes. Four animals were instrumented to record pulmonary arterial pressure, carotid arterial pressure, cardiac output, and arterial gas tensions. After control values were recorded, clenbuterol (0.8 μg/kg) was intravenously administered to each horse in each experiment group.

Following clenbuterol administration, non‐elastic resistance of the lung or pulmonary resistance significantly decreased, 33.6% reduction at 10 min post‐clenbuterol. Pulmonary resistance remained lowered during the entire procedure and showed no tendency of returning toward control values by 3 h post‐clenbuterol. Within 30 sec following clenbuterol injection carotid arterial pressure decreased (mean pressure decrease 28.2%). Accompanying the change in arterial pressure, the heart rate drastically increased, 99.0%. Both changes were transient and returned to control ranges within 2 min.

Clenbuterol appears to be effective in reducing non‐elastic resistance of the lung, however intravenous administration to an animal with pre‐existing cardiovascular or cardiopulmonary disease should be avoided.
Lack of effect of multiple oral doses of meclofenamic acid on parturition in goats
Authors: COOKE R. G. , KNIFTON A.
Published: April 2008

Daily oral doses of 500 mg meclofenamic acid, a potent inhibitor of prostaglandin biosynthesis, had no observable effects on parturition in goats. These findings are contrary to previous studies in the goat and other animals, but may be a result of the route of meclofenamate administration.
Plasma levels of valproic acid and its metabolites during continued treatment in dogs
Authors: LÖSCHER W.
Published: April 2008

Dogs were treated with the anti‐epileptic drug valproic acid (VPA) for 2 weeks in order to determine whedier therapeutic plasma levels could be maintained. VPA (as the sodium salt) was administered in a dosage of 170–180 mg/kg/day divided into three equal doses in the form of enteric‐coated tablets. Due to the rapid elimination of this drug in dogs, therapeutic plasma levels were reached only intermittently. However, the concentrations maintained may be sufficient for anti‐epileptic therapy in dogs because the lower plasma protein binding of VPA in this species gives rise to higher central concentrations compared with man. Furthermore, some VPA metabolites previously shown to exert anticonvulsant activity (2‐en‐VPA and 3‐keto‐VPA) were found in relatively high concentrations in dog plasma.

We would recommend the dosages used in this study as a basis for assessment of VPA in the treatment of canine epilepsy.
Autonomic and non‐autonomic control of cardiovascular function in stress‐sensitive pigs
Authors: GREGORY N. G. , WOTTON S. B.
Published: April 2008

The T‐wave characteristics, heart rate, stroke volume, cardiac output and blood pressure were examined in acidosis‐prone Pietrain and acidosis‐resistant Gloucester Old Spot pigs, before and after autonomic blockade with propranolol, atropine and phentolamine. Assessments were made at normal arterial blood pH and pCO2, and at either the same age or live weight in the two breeds. T‐wave amplitude was influenced by α‐adrenergic activity in the absence of β‐adrenergic and parasympathetic receptor activation.

The initial cardiac output was 25% greater in the Pietrains, and 75% of this breed difference was due to autonomic factors. Myocardial chronotropic responsiveness to noradrenaline was similar in the two breeds. Initial blood pressure was greater in the Gloucester Old Spots because of a non‐autonomic factor, and vasopressor responsiveness to noradrenaline was greater in the Gloucester Old Spots.

Although acidosis‐prone pigs may be afforded some degree of protection from a sympathetic crisis by having a low vasopressor responsiveness to adrenoreceptor stimulation, enhanced catecholamine output is the likely cause of their stress‐induced myocardial lesions. A high catecholamine output may also account for the reduced body fatness in this type of pig.
The determination of propiopromazine in animal tissue
Authors: OLLING M. , STEPHANY R. W. , RAUWS A. G.
Published: April 2008

A thin‐layer chromatographic method for the determination of the veterinary tranquillizer propiopromazine (Combelen®) in slaughter pigs is described. Propiopromazine residue depletion from the kidney occurs with different rates in sows and in castrated boars. In the liver residues increase over at least 24 h after intramuscular administration, in accordance with the distribution pattern of phenothiazine tranquillizers.
Effects of tryptamine antagonists on the anaphylactic contractions of the bovine pulmonary smooth muscles
Authors: OGUNBIYI P.O. , EYRE P.
Published: April 2008

Calves were sensitized with horse plasma (H.P.), 0.2 ml/kg, i.v., and H.P. (0.2 ml/ kg) in Freund's complete adjuvant, s.c. The latter injection was repeated 1 week later and the animals were killed 10 days after the second injection. Spirally cut strips of pulmonary artery and vein and the trachealis muscle from the sensitized calves contracted to 5‐hydroxytryptamine (5‐HT) and specific antigen (horse plasma). Antigen‐induced contractions of the pulmonary smooth muscles were significantly blocked (P<0.05) by the 5‐HT antagonists, methysergide and ketanserin. The trachea, however, appeared less sensitive to the antagonists than the pulmonary vessels.

The results suggest that 5‐HT participates in the pulmonary anaphylactic reactions of cattle and that ketanserin may be useful in suppressing bovine pulmonary hypersensitivities.
Effect of premedication with acetylpromazine on the disposition kinetics of thiopental
Authors: BAGGOT J. D. , TOUTAIN P. L. , BRANDON R. A. , ALVINERIE M.
Published: April 2008

This study was performed to determine whether premedication with acetyl‐promazine alters the disposition kinetics of thiopental in normal dogs. Based on nonlinear least squares regression analysis of the plasma concentration‐time data obtained in individual dogs, a three‐compartment open model was selected to describe the pharmacokinetic behavior of thiopental. While clinically premedication appears to delay time of awakening from thiopental anesthesia, statistical comparison (Student's t‐test for paired data) of pharmacokinetic terms showed no significant difference. This may be largely attributed to wide individual variation in each parameter. The rate of change in volume of distribution at zero time (mean ± SD, n = 7), which is a parameter that might have been expected to vary significantly, was 97 ± 106 ml/min‐kg for thiopental alone and 77 ± 60 ml/min‐kg following acetylpromazine premedication. Body clearance of thiopental was 1.96 ± 0.59 ml/min‐kg in dogs without premedication and 1.55 ± 0.49 ml/min‐kg following acetylpromazine. By relating observed time of awakening to plasma concentrations of thiopental it was determined that awakening from anesthesia occurred at a concentration of 20 μg/ml whether or not the dogs were premedicated. It can only be concluded that while premedication with acetylpromazine appears to delay time of awakening from anesthesia, it does not change the disposition kinetics of thiopental or affect the plasma concentration at the observed time of awakening.
Furazolidone concentrations in plasma, milk and some tissues of Nubian goats
Authors: MUSTAFA A. I. , ALI B. H. , HASSAN T. , SATTI A. M.
Published: April 2008

Mustafa, A.I., Ali, B.H., Hassan, T. & Satti, A.M. Furazolidone concentrations in plasma, milk and some tissues of Nubian goats. J. vet. Pharmacol. Therap. 8, 190–193.

The concentrations of furazolidone (FZ) in plasma and milk were measured in goats treated orally with the drug at a dose of 10mg kg‐1 daily for 5 days. The maximum plasma concentrations obtained were 1.57 δ 0.52 μg ml‐1 (n = 5) 8 h after the first dose, and 2.13 δ 0.11 μg ml‐1 (n = 4) 6 h after the fifth dose. The maximum milk concentration was 0.88 δ 0.32 μg ml‐1 (n = 4) 8h following the administration of a single dose. Using a colorimetric method, FZ was not detectable in goats' liver or muscle after the recommended therapeutic dose (10 mgkg‐1, 5 days). However, using an HPLC method, the drug was detected 24 h after the treatment in the gluteal muscle and liver at concentrations of 0.2G δ 0.01 μg g‐1 (n = 5) and 0.10 δ 0.02μg g_1 (n = 5), respectively. The drug concentrations decreased significantly (P < 0.05‐0.01) at 3, 5 and 7 days after treatment, and no measurable concentrations were found after 10 days.

A. I. MustafaC, Department of Medicine, Pharmacology and Toxicology, Faculty of Veterinary Science, University of Khartoum, P.O. Box 32, Khartoum North, Sudan.
2‐(1,1‘‐biphenyl‐4‐yl)‐1,2,4‐triazole[5,1‐a] isoquinoline (L 14105), a potential orally active contragestational agent for the bitch: studies in the rat, hamster and dog
Authors: GALLIANI GIULIO , GUZZI UMBERTO , TARZIA GIORGIO , ASSANDRI ALESSANDRO
Published: April 2008

In the search for second generation post‐coital pregnancy terminating agents belonging to the class of 2‐phenyl‐triazole[5, l‐a]isoquinolines, the contragestational profile of (1, 1 ′‐biphenyI)‐4‐yl‐1, 2, 4‐triazole[5, l‐a]isoquinoline, referred to as L 14105, was investigated in hamsters, rats and bitches. Following subcutaneous or intramuscular administration in oily vehicles, L 14105 shows a very high anti‐fertility activity in the three animal species, being from 1.8 to 2.5 times more effective than the parent drug, DL 717‐IT. Unlike DL 717‐IT, L 14105 possesses a high activity when administered by the oral route. The results obtained in the bitch make it confirm its potential use as a new orally active agent for the interruption of unwanted pregnancies.
Antinociceptive activity and mechanism of action of detomidine
Authors: VIRTANEN RAIMO
Published: April 2008

The antinociceptive activity and mechanism of action of detomidine, a novel sedative‐analgesic, were studied in mice and rats. Xylazine and morphine were included in the studies for comparison. In both acetic acid‐induced writhing test in mice, and in tail flick test in rats, detomidine had potent, dose‐dependent antinociceptive effects with ED50 values of 0.06 and 0.2 mg/kg i.p., respectively. Both xylazine and morphine were clearly less potent than detomidine in these tests. The antinociceptive effect of detomidine was only inhibited by alpha‐2 antagonists (idazoxan, rauwolscine), which suggests that this action is mediated through stimulation of alpha‐2 adrenoceptors. The significance of these Findings for the use of detomidine in veterinary medicine is discussed.
Cardiovascular and allied actions of xylazine and atropine in the unanaesthetized goat
Authors: KOKKONEN U.‐M. , ERIKSSON L.
Published: April 2008

Kokkonen, U.‐M. & Eriksson, L. Cardiovascular and allied actions of xylazine and atropine in the unanaesthetized goat. J. vet. Pharmacol. Therap. 10, 11–16.

The cardiovascular effects of xylazine and atropine, separately and in combination, were studied in goats. Methylatropine was used to distinguish between the central and peripheral effects of atropine. Mean arterial blood pressure and heart rate were recorded, and the sedative effect and changes in respiration and salivation noted. Intravenous infusion of xylazine (2.4–80.0 μg/kg) decreased mean arterial blood pressure and heart rate in a dose‐dependent manner. Single intravenous injections of both atropine sulphate (0.1 mg/kg) and methylatropine bromide (0.05 mg/kg) increased blood pressure and heart rate. After methylatropine, tachycardia lasted twice as long as after atropine. Following atropin‐ization, a potentiated rise in mean arterial blood pressure was present during the infusion of xylazine (80 μg/kg). Xylazine‐induced bradycardia was reversed by both atropine and methylatropine. The action of atropine is presumed to be primarily peripheral because of the similar effects with methylatropine. Xylazine‐induced sedation was dose dependent. At the highest dose the goats were unable to stand for 30–60 min, respiration became irregular with periods of apnoea, and saliva started to drip a few minutes after infusion without increased salivation. Atropine had no visible effect on the sedation, pattern of respiration or saliva dripping effect of xylazine.
Sedative action of the α2‐agonist medetomidine in cats
Authors: STENBERG D. , SALVEN P. , MIETTINEN M. V.J.
Published: April 2008

Stenberg, D., Salven, P. & Miettinen, M.V.J. Sedative action of the α2‐agonist medetomidine in cats. J. vet. Pharmacol. Therap. 10, 319–323.

Medetomidine, a novel α2‐agonist drug intended for small animal sedation, was injected intramuscularly at dose rates of 0.02, 0.06 and 0.18 mg/kg. Xylazine (3.0 mg/kg) and saline were used for comparison. The five treatments were tested in a Latin square design in five cats. Treatments differed significantly in three‐way analysis of variance, medetomidine inducing an increase in drowsiness with a corresponding decrease in both aroused waking and sleep determined by polygraphical criteria. The duration of effect was dose‐dependent. The effect of 0.18 mg/kg medetomidine was comparable to 3.0 mg/kg of xylazine. The drugs also induced bradycardia.
Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves
Authors: SOBACK S.
Published: April 2008

Soback, S. Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves. J. vet. Pharmacol. Therap. 11, 155–162.

Cefoxitin pharmacokinetics and bioavailability were studied in unweaned calves. The antibiotic was administered to nine calves intravenously (i.v.), to seven calves intramuscularly (i.m.) at 20 mg/kg and to eight calves i.m. at 20 mg/kg together with probenecid at 40 mg/kg. Serum concentration versus time data were analysed using statistical moment theory (SMT). The i.v. data were also fitted by a linear, open two‐compartment model.

The elimination half‐life (t½) was 66.9 ± 6.9 min (mean ± SD) after i.v. and 81.0 ± 10.9 min after i.m. administration. The t1/2 increased to 125.5 ± 15.6 min by the co‐administration of probenecid. The total body clearance (ClT) was 4.88 ± 1.71 ml/min/kg and the volume of distribution (Vss) 0.3187 ± 0.0950 1/kg. The mean residence time (MRT) was 68.2 ± 12.3 min after i.v. and 118.6 ± 16.8 min after i.m. injection and increased to 211.5 ± 16.8 min by the coadministration of probenecid. The mean absorption time (MAT) was 50.6 min and the estimated bioavailability (F) of cefoxitin after i.m. administration was 73.8%. The cefoxitin protein binding ranged from 55.0 to 42.0% at concentrations from 2 to 50 μg/ml.

The MIC90 values for cefoxitin were 6.25 μg/ml for E. coli and Salmonella group B isolates, 3.13 μg/ml for Salmonella group C and D and Pasteurella multocida.

There were no statistically significant differences between the pharmacokinetic parameters calculated by SMT or compartmental analysis. SMT provided an additional independent parameter, the MRT, for characterization of drug disposition kinetics.
The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils
Authors: PYCOCK J. F. , ALLEN W. E. , PORTER D.J. , BOYD E. H.
Published: April 2008

Pycock, J.F., Allen, W.E., Porter, D.J., Boyd, E.H. The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils. J. vet. Pharmacol. Therap.11, 191–196.

Two independent assay systems were used to study the effect of three antibacterial preparations on in vitro morphology and chemotaxis of equine neutrophils. Incubation of neutrophils with high (200 μg/ml) and medium (20 μg/ml) concentrations of neomycin impaired their response to standard chemoattractants. Trimethoprim/sulfadoxine (0.4/2.0 μg/ml–40/200 μg/ml) and benzylpenicillin (0.25‐25 μg/ml) had no effect. Neutrophils collected from geldings 2 and 24 h after neomycin (5 mg/kg) administration had impaired responses to standard chemoattractants. Benzylpenicillin (13.2 mg/kg) had no effect.
Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) – a software program designed to determine intravenous drug dosage regimens for veterinary applications
Authors: RIVIERE J. E. , FRAZIER D. L. , TIPPITT W. L.
Published: April 2008

Riviere, J.E., Frazier, D.L. & Tippitt, W.L. Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) – a software program designed to determine intravenous drug dosage regimens for veterinary applications. J. vet. Pharmacol. Therap. 11, 390–396.

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a software program used to design individualized intravenous dosage regimens, determine concentration–time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual anima's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual anima's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration–time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration‐time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal. These calculations allow design of dosage regimens that maximize therapeutic efficacy and minimize toxicity to the patient as well as to decrease the incidence of drug residues in food animals.
Appetite‐modulating drugs in dwarf goats, with special emphasis on benzodiazepine‐induced hyperphagia and its antagonism by flumazenil and R° 15–3505
Authors: MIERT A.S.J.P.A.M. VAN , KOOT M. , DUIN C. T. M. VAN
Published: April 2008

In dwarf goats fasted for 2 h, i.v. administration of the benzodiazepine (BZ) agonists diazepam (60 μg/kg), brotizolam (2 and 4 μg/kg) and climazolam (100 μg/kg) induced hyperphagic effects, whereas i.v. injections of the BZ‐antagonist flumazenil (R°15–1788; 0.5 mg/kg), the anthelmintic ivermectin (0.1 mg/kg), the 5‐HT2 antagonist ritanserine (0.1 mg/kg), ACTH (10 μg/kg) and prednisolone (1 mg/kg) were inactive in a 30‐min feeding test. Both the BZ‐antagonist R°15–3505 (≤ 0.1 mg/kg) and the opiate receptor antagonist naloxone (0.1 mg/kg) had anorectic effects in dwarf goats given 30 min access to a palatable pelleted concentrate. The hyperphagic effects of climazolam and brotizolam were not antagonized by flumazenil, whereas similar doses of this drug completely reversed muscle incoordination and ataxia induced by much higher doses of these BZ‐agonists. In the combination experiments with naloxone and BZ‐agonists, naloxone antagonized the hyperphagic effects of both diazepam and brotizolam. Similarly, in the diazepam–R°15–3505 study, there was a significant effect of diazepam and a significant inhibition of this effect by R° 15–3505 (50 μg/kg). In the diazepam–ivermectin combination experiment no evidence for drug potentiation was found. These results and the mode of action of the above mentioned drugs are discussed in relation to feeding behaviour.
The effect of avilamycin in the control of stress‐induced post‐weaning diarrhoea in piglets
Authors: KYRIAKIS S. C.
Published: April 2008

Avilamycin, an oligosaccharide antibiotic with growth‐promoting properties in pigs, has proved to be effective in controlling stress‐induced post‐weaning diarrhoea in piglets, caused mainly by Escherichia coli. The present study includes two trials, in which 400 newly‐weaned piglets were used (200/trial). The following five different treatments were tested; 0, 40 and 80 p.p.m. avilamycin, 50 p.p.m. olaquindox and 100 p.p.m. apramycin. In each trial there were four pens (each with five females and five males) per treatment. Avilamycin when given at 80 p.p.m. reduced average daily diarrhoea score (ADDS) and mortality, and improved liveweight gain and feed conversion ratio (FCR), compared with the untreated controls, the 40 p.p.m. avilamycin and the 50 p.p.m. olaquindox (P < 0.05) treatments. The overall performance of 40 p.p.m. avilamycin and 50 p.p.m. olaquindox was similar. The results indicate that avilamycin at the dose level of 80 p.p.m. in the starter feed can control post‐weaning diarrhoea of piglets and prevent loss of productivity. Nevertheless, the antibiotic apramycin, whose spectrum of activity is mainly against the Gram‐negative bacteria, given at the therapeutic level of 100 p.p.m., was more effective than any other experimental treatment (P < 0.05), except for ADDS and FCR which were not significantly different from that of avilamycin 80 p.p.m.
The pharmacokinetics and locomotor activity of alfentanil in the horse
Authors: PASCOE P. J. , BLACK W. D. , CLAXTON J. M. , SANSOM R. E.
Published: April 2008

The pharmacokinetics of alfentanil were investigated in the horse. Four doses of alfentanil (4, 10, 20 and 40 μg/kg) were given to four horses at different times and their locomotor activity monitored. Doses of 20 and 40 μg/kg produced a significant increase in locomotor activity. The plasma concentrations of alfentanil were measured in six standing horses and the pharmacokinetics calculated. It was found that the decay curves were best described by a bi‐exponential equation. The elimination half‐life (t1/2ß) was 21.65 ± 3.99 min and the clearance (CI) was 14.1 ± 0.7 ml/kg/min. The same horses were anaesthetized with xylazine‐ketamine and maintained with halothane in oxygen for the first experiment and isoflurane in oxygen for the second experiment. The pharmacokinetics were again calculated from measured plasma alfentanil concentrations. There were significant differences between the kinetics in the conscious and the anaesthetized animals but there were no significant differences in alfentanil kinetics between the two anaesthetic agents. The t1/2 for alfentanil under halothane and isoflurane anaesthesia were 55.95 ± 20.77 and 68.03 ± 23.22 min, respectively, and the CI values were 14 ± 1.7 and 13.6 ± 1.32 ml/kg/min.
A comparison of the sedative effects of three α2‐adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse
Authors: ENGLAND G. C. W. , CLARKE K. W. , GOOSSENS L.
Published: April 2008

The sedative effects of a new α2‐adrenoceptor agonist, romifidine, were compared with those of xylazine and detomidine. Five horses were treated with two doses of romifidine (40 μg/kg body weight and 80 μg/kg body weight), two doses of detomidine (10 μg/kg body weight and 20 μg/kg body weight) and one dose of xylazine (1 mg/kg body weight) given by intravenous injection using a Latin‐square design.

The dose of 80 μg/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20 μg/kg detornidine, although at these doses both xylazine and detomidine had a shorter action. Detomidine 20 μglkg and xylazine both produced greater lowering of the head and a greater degree of ataxia than romifidine at either dose. Romifidine produced sedation similar to that of the other drug regimes. The effect upon imposed stimuli was similar.
A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection
Authors: PAPICH M. G. , KORSRUD G. O. , BOISON J. O. , YATES W. D. G. , MACNEIL J. D. , JANZEN E. D. , COHEN R. D. H. , LANDRY D. A.
Published: April 2008

The disposition of an aqueous suspension of procaine penicillin G (300 000 U/ mL) was studied in feedlot steers. Four groups of three steers were used. Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24 000 U/kg (group 1) or of 66 000 U/kg (group 2). The injection on the last day was administered in the gluteal muscle. Steers in group 3 (i.m. neck injection) and group 4 [subcutaneous (s.c.) injection] each received a single dose of procaine penicillin G at a dose of 66 000 U/kg.

From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals. The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin.

The maximum plasma concentration (Cmax) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups. Group 4 single s.c. injections produced a lower mean Cmax (1.85 ± 0.27 ng/mL) than the mean Cmax (4.24 ± 1.08 μg/mL) produced in group 3 by i.m. injections into the neck muscle or the mean Cmax (2.63 ± 0.27 μg/mL) produced in group 2 by i.m. injections into the gluteal muscle. However the mean Cmax produced by i.m. injections into the neck muscles (group 3) was higher than the mean Cmax produced by i.m. injections into the gluteal muscle (group 2). Additionally, the disappearance t½, was longer (18.08 h) in group 4 following the s.c. injection and shorter (8.85 h) in group 3 following the i.m. neck injection, than the t½ following administration of the same dose i.m. into the gluteal muscle (15.96 h) in group 2. In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66 000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration (MIC) for penicillin G of 1.0 μg/mL as compared to doses of 24 000 U/kg.
Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken*
Authors: ANADÓN A. , BRINGAS P. , MARTINEZ‐LARRANAGA M. R. , DIAZ M. J.
Published: April 2008

Anadón, A., Bringas, P., Martinez‐Larrañaga, M.R., Diaz, M.J. Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken. J. vet. Pharmacol Therap.17, 52–58.

The pharmacokinetic properties of chloramphenicol were determined in broiler chickens after two sinSle oral doses (30 and 50 mg/kS body weight) and after a single intravenous (i.v.) dose (30 mg/kg body weight). After oral and i.v. administration, the plasma concentration‐time graph was characteristic of a two‐compartment open model. After oral administration (30 and 50 mg/kg). chloramphenicol was absorbed rapidly (time to maximal concentration of 0.72 or 0.60 h) and eliminated with a mean half‐life (t½β) of 6.8 7 or 7.41 h, respectively. The bioavailability was 29% at 30 mg/kg chloramphenicol and 38% at 50 mg/kg chloramphenicol. Concentrations greater than 5 (m̈g/ml were achieved at 15 min and persisted up to 2 or 4 h post‐administration, respectively. Statistically significant differences between the two routes of administration were found for the pharmacokinetic variables, half‐lives of both distribution and elimination phases (t½αt½β) and apparent volume of distribution [Vd(area)]. The meant½β of chloramphenicol and i.v. administration was 5.23 h. Chloramphenicol was extensively metabolized into dehydrochloramphenicol (DH‐CAP), nitrophenylaminopropanedione (NPAP) and nitroso‐chlorampheni‐col (NO‐CAP) derivatives. Residues of chloramphenicol (CAP) and the three metabolites DH‐CAP, NPAP and NO‐CAP in kidney, liver and muscle were measured in chickens that received an oral dose of 50 mg/kg once daily for 4 days. The results indicate that CAP and DH‐CAP residues were cleared slowly and were at or below the detection limit of 0.005 m̈g/ml within 12 days after dosing. However, at the time of slaughter (12 days), the NPAP and NO‐CAP residues were detected in the tissue.
Pharmacokinetics of cyclosporine in woodchucks and Pekin ducks
Authors: VADEN S. L. , CULLEN J. M. , RIVIERE J. E.
Published: April 2008

The purpose of this study was to evaluate the pharmacokinetics of cyclosporine (Cy) in woodchucks (Marmota monax) and Pekin ducks. These data are needed to design rational dosing regimens. Pharmacokinetic parameters were calculated from blood concentration‐time data obtained following intravenous (i.v.) administration of 10 mg/kg body weight to woodchucks and Pekin ducks. Whole blood samples were collected in EDTA and assayed using a commercially available radioimmunoassay kit that employs a monoclonal antibody specific for Cy. The blood concentration‐time profile best Dtted an open, two‐compartmental model in Pekin ducks. Compartmental analysis of data in woodchucks did not adequately describe the data. When non‐compartmental pharmacokinetic analysis of the data was performed, the resulting mean (± SD) pharmacokinetic parameters in woodchucks and Pekin ducks, respectively, were as follows: volume of distribution at steady‐state, 2.9 (± 0.8) and 2.7 (± 0.2) L/kg; systemic clearance, 10.2 (± 2.8) and 28.6 (± 6.1) mL/kg/min; mean residence time, 4.8 (± 1.1) and 1.6 (± 0.3). These data suggest that Pekin ducks clear Cy at a faster rate than do woodchucks and that a greater dose of Cy should be administered to Pekin ducks in order to achieve adequate immunosuppression.
A non‐invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses
Authors: TOUTAIN P.L. , LASSOURD V. , COSTES G. , ALVINERIE M. , BRET L. , LEFEBVRE H.P. , BRAUN J.P.
Published: April 2008

The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by l.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady‐state volume of distribution was 0.050 ± 0.0115 L/kg and the plasma half‐life was 112 ± 18 min. After CK i.m. administration, the half‐life of the terminal phase was 11.8 ± 5.3 h indicating a flip‐flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 ± 109 U/L after the neck administration and 873 ± 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 ± 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 ± 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30–60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24–48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non‐invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.
Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses
Authors: LANDONI M.F. , LEES P.
Published: April 2008

The bioavailability of S(+) and R(‐) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil‐based paste containing micronised rac‐KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil‐based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intravenous administration of rac‐KTP, S(+) enantiomer concentrations exceeded those of the R(‐) enantiomer. For S(+) and R(‐)KTP. respectively, pharmacokinetic parameters were, t1/2β 0.99 ± 0.14 h, 0.70 ±0.13 h;C/B 0.56±0.09,0.92±0.20 L/h/kg; Vd(ss), 0.53 ±0.11.0, 61±0.10L/kg. Following oral administration of rac‐KTP as the oil‐based paste to horses with free access to food, there were no detectable concentrations in plasma in three animals at any sampling time, while a fourth animal showed very low concentrations at two sampling times only. In the two remaining horses very low but detectable concentrations were present for 5 h. In the horses with restricted access to food, rac‐KTP paste administration produced higher concentrations in plasma. However, bioavailability was very low, 2.67 ± 0.43 and 5.75 ± 1.48% for R(‐) and S(+)KTP, respectively. When administered as pure drug substance in hard gelatin capsules, absorption of KTP was fairly rapid, but incomplete. Bioavailability was 50.55 ± 10.95 and 54.17 ±9.9% for R(‐) and S(+)KTP, respectively.

This study demonstrates that rac‐KTP had a modest bioavailability when administered as a micronised powder in hard gelatin capsules to horses with restricted access to food. When powder from the same source was administered as an oil‐based paste, it was for practical purposes not bioavailable, regardless of the feeding schedule.