bluuebunny/crossref_metadata_2025 huggingface dataset:
Xylazine‐induced mydriasis in rats and its antagonism by α‐adrenergic blocking agents
Authors: HSU WALTER H. , LEE PERNG , BETTS DANIEL M.
Published: April 2008

Pupillary response to xylazine (10–300 μg/kg, i.v.) norepinephrine (1–30 μg/kg, i.v.) and atropine (3–100 μg/kg, i‐v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose‐dependent mydriasis which was antagonized by a selective α2‐adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). A non‐selective adrenergic blocking agent, phentolamine (2.5 mg/kg, i.v.) was less effective in antagonizing this effect of xylazine. A selective α1‐adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine‐induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine‐induced mydriasis. Atropine also induced a dose‐dependent mydriasis which was not affected by yohimbine pre‐treatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the α2‐adrenergic receptors in the iris and CNS.
Pharmacokinetic studies of theophylline in dogs
Authors: McKIERNAN B. C. , NEFF‐DAVIS C. A. , KORITZ G. D. , DAVIS L. E. , PHERIS D. R.
Published: April 2008

The pharmacokinetics of theophylline were investigated in dogs following intravenous, single oral, and multiple oral doses of aminophylline. Mean half‐life (t1/2) of theophylline following single intravenous administration was 5.7 h and the apparent specific volume of distribution (V'd area) was 0.82 litre/kg. The bioavailability of theophylline was high (91%) following oral administration of aminophylline tablets and the absorption half‐life (t1/2 ab) was 0.4 h.

Theophylline plasma concentrations observed following repeated oral administration of aminophylline tablets were somewhat greater than predicted. This suggests that theophylline plasma concentrations should be monitored and the dosage regimen individually adjusted in critically ill animals.
Warfarin in the dog: pharmacokinetics as related to clinical response
Authors: NEFF‐DAVIS CAROL A. , DAVIS LLOYD E. , GILLETTE EDWARD L.
Published: April 2008

Warfarin was administered intravenously (i.v.) as a single dose of 1.5 mg/kg to healthy dogs and the pharmacokinetic parameters were investigated. Elimination could be described by a one‐compartment open model. Values for the elimination half‐life and apparent specific volume of distribution were 14.5 ± 4.1 h and 0.22 ± 0.04 litre/kg, respectively. Oral maintenance doses were calculated from the data collected following i.v. administration and administered every 12 h for a total of five doses after an initial i.v. loading dose of 1.5 mg/kg. Prothrombin times increased from a control value of 8.6 ± 0.3 sec to 55.2 ± 5.2 sec over a period of 96 h. Prothrombin time returned to control values by 62 h after withdrawal of the drug. We propose a dosage regimen of warfarin for anticoagulant therapy in the dog of 0.22 mg/kg to be given orally every 12 h. Prothrombin time should be monitored during therapy and the dose of warfarin modified according to the degree of suppression of coagulation factors desired.
Pharmacokinetics and dosage of chlorpromazine in goats
Authors: NAWAZ MUHAMMAD
Published: April 2008

Pharmacokinetic parameters which describe the distribution and elimination of chlorpromazine in goats were determined. Following the intravenous administration of a single dose (2.5 mg/kg), disposition of the drug was described in terms of the biexponential expression Cp= Ae‐αt+ Be‐βt. Based on total (free and bound) chlorpromazine levels in plasma, pseudo‐distribution equilibrium was rapidly attained, and the elimination half‐life was 1.51 ± 0.48 h (mean ± SD, n = 8). Total body clearance, which is the sum of all clearance processes, was 80 ± 25 ml/min/kg. The curves of an animal representative of the group, based on individual rate constants associated with the two‐compartment open model, showed that at 5 h after drug administration 8% and 6% of the dose were present in the peripheral and central compartments, respectively. The kinetic parameters of chlorpromazine determined at a dosage level of 10 mg/kg body weight in six goats showed that the drug followed first‐order kinetics and kinetic parameters were similar after both dose levels. Based on these findings and therapeutic plasma levels, a satisfactory intravenous regimen should be 2.0 – 3.5 mg/kg and the drug action will persist for 5–6 h.
Effect of Solcoseryl® on the clinical course of experimental Escherichia coli‐endotoxin mastitis
Authors: ZIV G. , JÖCHLE W.
Published: April 2008

Experimental Escherichia coli‐endotoxin mastitis was induced in a single quarter in twenty‐eight cows. The inflamed quarters of six of the cows were treated with 50 mg Solcoseryl® infusion in an oil base starting 4–6 h after endotoxin infusion, and four additional infusions were given at 12‐h intervals. The inflamed quarters of eight of the cows were similarly treated with 200 mg Solcoseryl® whereas the remaining fourteen cows served as control. Solcoseryl® treatment did not alter the systemic or local course of acute mastitis. Local reaction, as assessed by the California Mastitis Test (CMT), however, subsided considerably sooner in quarters treated with Solcoseryl®, and the effect of Solcoseryl® in hastening udder tissue repair processes appeared to be dose dependent. The 200 mg dose of Solcoseryl® resulted in pre‐endotoxin CMT scores as early as 6 days after endotoxin infusion.
Sulfamethazine residues in swine
Authors: BIEHL L. G. , BEVILL R. F. , LIMPOKA M. , KORITZ G. D.
Published: April 2008

Two possible causes of violative sulfonamide residues in swine were studied. To determine if sulfamethazine accumulated in the tissues of swine when the drug was administered in feed, the rates of plasma drug disappearance following a single oral dose and continuous feeding of the drug were compared. The rate of plasma drug disappearance was not significantly different (α= 0.05) when the two methods of drug dosing were compared. When feed containing 2 μg sulfamethazine/gm was fed to swine during a 7—day period preceding slaughter, the animal's liver contained violative residues. Violative concentrations of sulfamethazine were detected in the livers, kidneys, and skeletal muscle of swine which consumed feed containing 8 μg sulfamethazine/gm.
Fenbendazole and thiabendazole in cattle: partition of gastrointestinal absorption and pharmacokinetic behaviour
Authors: PRICHARD R. K. , STEEL J. W. , HENNESSY D. R.
Published: April 2008

Fenbendazole (FBZ) and thiabendazole (TBZ) were administered intraruminally with a single dose of an indigestible marker, chromium ethylenediaminetetra‐acetate (Cr‐EDTA), to cattle fitted with gastrointestinal cannulae. The amounts of anthelmintic leaving the rumen, abomasum and terminal ileum in digest a were derived by compartmental analysis of Cr‐EDTA concentrations and integration of benzimidazole concentrations.

TBZ was absorbed much more rapidly from the rumen than FBZ and only about 12% of the dose left the rumen in digesta compared with 30% of the FBZ. Approximately 10% and 8% of the TBZ dose appeared at the pylorus and terminal ileum, respectively. Of the above amounts, 9% in the abomasum and practically 100% in the ileum was present as 5‐OH‐TBZ, indicating that metabolites of absorbed TBZ were recycled to the gastrointestinal tract. Twenty‐eight percent and 52% of the FBZ appeared at the pylorus and terminal ileum, respectively, indicating a substantial recycling of absorbed drug to the small intestine. It is suggested that biliary secretion of both TBZ and FBZ and their metabolites may contribute to this recycling.

Maximal concentrations of TBZ occurred in plasma in 4 h compared with about 24 h for FBZ. TBZ and metabolites were excreted in urine much more rapidly than were FBZ and metabolites. In plasma and in each of the gastrointestinal compartments, FBZ persisted much longer than did TBZ. It was concluded that slower absorption and excretion and more extensive recycling to the gastrointestinal tract of FBZ, than of TBZ, contribute markedly to its greater potency against helminths.
Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves
Authors: SCHIFFERLI D. , GALEAZZI R. L. , NICOLET J. , WANNER M.
Published: April 2008

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half‐lives in the β‐elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 ± 1.36 h and 7.16 ± 1.17 h, mean ± SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 μg/ml were maintained with both formulations during 12–24 h but were only above 4 μg/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t1/2a1= 0.27 h) and a slower one (t1/2a2= 10.90 h) responsible for the delayed elimination half‐life after this route of application (t1/2β= 9.83 ± 1.35 h). Mean serum concentrations reached a maximum level of 3.01 ± 0.72 μg/ml at 4.01 ± 2.84 h and decreased to 0.5 μg/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 ± 1.37 μg/ml was achieved at 9.16 ± 1.99 h and the mean concentration was still above 0.5 μg/ml after 48 h. The elimination half‐life (t1/2β= 10.66 ± 3.15 h) reflected the slow absorption step (t1/2a2= 10.15 h) following that responsible for the initial faster absorption (t1/2a2= 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens
Comparative pharmacokinetics of chlortetracycline in milk‐fed versus conventionally fed calves
Authors: BRADLEY B. D. , ALLEN E. H. , SHOWALTER D. H. , COLAIANNE J. J.
Published: April 2008

Plasma and tissue concentration and pharmacokinetics of chlortetracycline (CTC) was determined in milk‐fed and conventionally fed Holstein calves. A two‐compartment open model was used after a single intravenous dose (11 mgn CTC/kg body weight). There were no significant differences between dietary treatments. The drug was rapidly distributed from plasma into the peripheral compartment but was slowly eliminated, with detectable concentration of CTC continuing for 72 h after dosing. A single‐compartment model was used after a single oral dose (22 mg CTC/kg body weight). All but four of the kinetic parameters were significantly different for the two dietary treatments. Milk‐fed calves had a larger area under the plasma level curve, a larger fraction of the dose absorbed, a smaller volume of distribution and a smaller overall body clearance rate. Estimated recovery of CTC in the urine of the milk‐fed calves was greater, regardless of route of administration. The concentration of CTC in tissues following an oral dose was greatest in kidney, followed by liver, heart, skeletal muscle, spleen and brain. Tissue depletion of CTC closely paralleled the decline in plasma concentration.
Dexamethasone in cattle: pharmacokinetics and action on the adrenal gland
Authors: TOUTAIN P. L. , BRANDON R. A. , ALVINERIE M. , GARCIA‐VILLAR R. , RUCKEBUSCH Y.
Published: April 2008

The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base‐line and ACTH‐stimulated cortisol concentrations, before and following DXM administration.

Following intravenous administration, the disposition kinetics of both formulations were described by a two‐compartment open model. The half‐times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension.

The mean control plasma cortisol concentration was 8.8 ± 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2–4 h (intramuscular), concentrations were negligible; 24–72 h and 48–96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH‐stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.
Pharmacokinetics of polymyxin B administered via the bovine mammary gland
Authors: ZIV G. , SCHULTZE W. D.
Published: April 2008

Polymyxin B was infused into normal, chronically inflamed, and acutely inflamed quarters of the mammary gland of lactating cows at dosages ranging between 1 and 2 million units (100–200 mg) per quarter. Samples of milk from treated and non‐treated quarters, jugular venous blood, subcutaneous abdominal (mammary) venous blood, and urine were collected at intervals after treatment and were assayed using microbiological test methods for polymyxin B concentrations. The drug was not absorbed from normal and chronically inflamed quarters; more than 90% of the infused dose was recovered in milk within 24 h after treatment, and drug residues were detected up to the ninth milking. Drug concentrations in milk from acutely inflamed quarters were significantly lower than in milk from normal quarters; 55% of the infused dose was recovered in the milk within 24 h after treatment. The drug was detected in milk from non‐treated quarters, in blood from the subcutaneous abdominal vein, and in the urine during 36–48 h after acutely inflamed quarters were infused with the drug. These data indicate that polymyxin B is well distributed throughout, and is absorbed to a significant degree into the systemic circulation from the acutely inflamed udder.
Pharmacokinetics of chloramphenicol in non‐lactating cattle
Authors: ANDERSON K. L. , NEFF‐DAVIS C. A. , DAVIS L. E. , KORITZ G. D. , NELSON D. R.
Published: April 2008

The pharmacokinetics and bioavailability of a formulation of chloramphenicol base in propylene glycol were determined following administration of single intravenous (i.v.) and subcutaneous (s.c.) 50 mg/kg doses of chloramphenicol to six non‐lactating Holstein cows.

Mean serum concentrations of chloramphenicol following i.v. administration of 50 mg/kg declined rapidly from a peak of greater than 100 μg/ml to 6.9 μg /ml at 12 h after administration.

Serum concentrations were not detectable at 24 h after administration. The curve of serum concentrations vs time was characteristic of a two‐compartment open model. Mean i.v. data gave a biological half‐life of 4.3 h and a volume of distribution of the central compartment of 0.44 1/kg. Serum concentrations of chloramphenicol following s.c. administration of 50 mg/kg rose slowly to a broad peak near 20 μ g/ml from 3 to 8 h after administration and then declined. These data were also analysed according to a two‐compartment open model. The biological half‐life was 4.2 h and the volume of distribution of the central compartment was 0.50 1/kg.

Significant adverse reactions, including acute collapse, intravascular haemolysis and haemoglobinuria, were observed in cows when dosed i.v. Cows dosed s.c. exhibited local reactions at injection sites.

The disadvantages of administration of 50 mg/kg doses of chloramphenicol base in propylene glycol appear to be significant and may outweigh the potential advantages of parenteral use of the drug as presently formulated.
Pharmacokinetic studies of theophylline in cats
Authors: McKIERNAN B. C. , KORITZ G. D. , DAVIS L. E. , NEFF‐DAVIS C. A. , PHERIS D. R.
Published: April 2008

The pharmacokinetics of theophylline were determined in adult cats and the data were fitted to a two‐compartment model. Single intravenous and multiple oral doses of aminophylline were used. The mean plasma theophylline half‐life (t1/2) following the single intravenous dose was 7.8 h and the mean apparent specific volume of distribution (V'd(area)) was 0.46 l/kg. The absorption half‐life (t1/2ab) was 0.5 h and the bioavailability was 96% following oral administration. There was excellent agreement between the predicted and observed plasma theophylline concentrations following multiple oral doses.
Clinical pharmacology of tiamulin in ruminants
Authors: ZIV G. , LEVISOHN S. L. , BAR‐MOSHE B. , BOR A. , SOBACK S.
Published: April 2008

Median values for the minimum inhibitory concentrations (MIC) of tiamulin for Mycoplasma and Acholeplasma isolated from ruminants were 0.05 μg/ml and 0.025 μg/ml, respectively. These values were close to the MIC values of tylosin and considerably lower than the respective values for spectinomycin, spiramycin and oxytetracycline.
The effect of antibiotics on mannose‐resistant haemagglutination by K88‐ and K99‐positive Escherichia coli strains
Authors: SØGAARD H. , LARSEN J. L.
Published: April 2008

Five E. coli strains carrying K99 antigen isolated from the intestines of calves which had succumbed to diarrhoea and six K88‐positive strains isolated from fatal cases of diarrhoea in piglets were examined for their mannose‐resistant haemagglutination (MRHA) capacity against pig erythrocytes. The bovine strains showed a geometric mean MRHA‐titre of 1/18 and the porcine strains one of 1/45. Similar experiments were carried out after addition of the following antibiotics in doubling dilutions: ampicillin, chloramphenicol, colistin, dihydro‐streptomycin, gentamicin, neomycin, polymyxin B and oxytetracycline. Colistin and polymyxin B had a marked concentration‐dependent inhibitory effect on MRHA. Neomycin and gentamicin also inhibited MRHA but to a lesser degree. Chloramphenicol, dihydrostreptomycin and oxytetracycline showed no effect. With ampicillin, a trend was found for the ratio values to be inversely proportional to the concentration. This suggests that this antibiotic has an enhancing effect on the haemagglutination.
Pharmacokinetics of chloramphenicol in the neonatal horse
Authors: BRUMBAUGH GORDON W. , MARTENS RONALD J. , KNIGHT HUMPHREY D. , MARTIN MICHAEL T.
Published: April 2008

Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first‐order elimination. Mean pharmacokinetic values were: zero‐time serum concentration (C0) = 36.14 μg/ml (±14.80); apparent specific volume of distribution (Vd) = 1.614 1/kg (±0.669); and elimination rate constant (K) = 0.7295 h‐1 (±0.3066) which corresponds to a biological half‐life (t1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.

A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.
Halothane‐sparing effect of xylazine in dogs and subsequent reversal with tolazoline
Authors: TRANQUILLI W. J. , THURMON J. C. , CORBIN J. E. , BENSON G.J. , DAVIS L. E.
Published: April 2008

Halothane MAC (the minimum alveolar concentration of halothane to produce anaesthesia in 50% of the animals tested) was determined to be 0.92 ± 0.16 volumes % in eight English Pointer dogs. Alterations in halothane MAC induced by an intravenous bolus of xylazine (1.1 mg/kg) and then tolazoline (5 mg/kg) was determined in each dog following control (halothane MAC) measurement. Following xylazine administration, MAC significantly decreased to 0.57 ± 0.023%. Immediately following determination of the xylazine‐halothane MAC value in each dog, tolazoline was administered and the halothane requirement (MAC) was again assessed. Halothane MAC significantly increased to 1.24 ± 0.036%. Tolazoline administration induced immediate arousal in the xylazine‐halothane anaesthetized dogs requiring a rapid increase in halothane concentration to maintain anaesthesia. Thus, the administration of tolazoline, an alpha adrenergic antagonist, following xylazine administration significantly increased the anaesthetic requirement (MAC) of halothane. Xylazine, an alpha 2 adrenergic agonist, decreased halothane anaesthetic requirement (MAC) in the eight dogs studied. These results are consistent with the hypotheses that stimulation of central alpha 2 receptors is the mechanism by which xylazine produces sedation and that inhibition of CNS excitatory neurotransmitter release decreases halothane anaesthetic requirement. In contrast, the increase in halothane requirement and arousal from xylazine‐halothane anaesthesia that occurred following i.v. tolazoline administration indicates an increase in CNS excitatory neurotransmitter activity.
The effects of combinations of selected antibiotics on the growth of Corynebacterium equi
Authors: PRESCOTT J. F. , NICHOLSON V. M.
Published: April 2008

The minimal inhibitory concentrations of penicillin G, ampicillin, gentamicin, erythromycin and rifampicin were determined for nine strains of Corynebacterium equi. The effect of combinations of any two of these antibiotics on the killing of these strains was determined at antibiotic concentrations achievable in horses using recommended drug dosages (ampicillin 4.0 μg/ml, gentamicin 1.0 μg/ml and erythromycin 0.25 μg/ml). Penicillin G was used at 4.0 μg/ml and rifampicin at 0.063 μg/ml. The combinations of gentamicin with erythromycin or rifampicin gave antagonistic effects on killing compared to either drug alone. Combinations of erythromycin with rifampicin or penicillin showed synergistic effects, as did penicillin‐gentamicin. All other combinations, and a triple combination of penicillin‐rifampicin‐erythromycin, showed additive effects only.
A preliminary study on the use of carbenicillin in snakes
Authors: LAWRENCE K. , NEEDHAM J. R. , PALMER G. H. , LEWIS J. C.
Published: April 2008

The results of a 10 year survey on the in vitro antibiotic resistance patterns of Pseudomonas spp. isolated from clinically ill reptiles, showed a high degree of sensitivity to carbenicillin. On the basis of sensitivity testing, carbenicillin was used to treat nine snakes of four different species, with confirmed Pseudomonas infections. Plasma carbenicillin levels were assayed, by a microbiological agar diffusion technique, at intervals of time after a single intramuscular injection at a dose rate of 400 mg/kg. Peak plasma levels of 177 and 270 μg/ml were reached 1 h after the initial injection and therapeutic levels persisted for at least 12 h. This initial study indicated that a suggested dose regime in snakes, derived by extrapolation from mammalian dosages, of 100‐125 mg/kg daily was insufficient to produce plasma levels of sufficient magnitude and duration to effectively treat Pseudomonas infections in snakes.
Standardization of an experimental disease model of Streptococcus zooepidemicus in the equine
Authors: VARMA KANWAL J. , POWERS THOMAS E. , POWERS JEAN D. , SPURLOCK SHAUNA L.
Published: April 2008

A reproducible experimental disease model in horses using Streptococcus zooepidemicus was developed. An intravenous challenge dose of 1 × 1010 colony‐forming units (CFU), followed 24 h later with another challenge of 1 × 108 CFU of Strep, zooepidemicus produced the desired disease model. The disease was characterized by depression, pyrexia, anorexia, abnormal lung sounds, inflammation of joints, moderate to severe lameness, gradual loss of condition and emaciation. The effects of the disease on hematology, serum chemical profile and different protein fractions were studied. The disease state had no effect on serum glucose, sodium, potassium, chloride, urea nitrogen, creatinine, uric acid, calcium, phosphorus and enzymes SGOT or SGPT. However, the alkaline phosphatase showed a gradual decline. The serum iron levels dropped markedly and remained low to the last day of observations (post‐infection day, PID 13). On serum protein electrophoresis, the albumin showed a gradual decrease; whereas, alpha II, beta and gamma globulin levels rose suggesting an immune response. The elevation of rectal temperatures and white blood cell counts related well with clinical observations. The serum iron levels proved very helpful in predicting the severity of clinical signs and often dropped before the onset of clinical signs and pyrexia.
Effect of antidotal N‐acetylcysteine on the pharmacokinetics of acetaminophen in dogs
Authors: OMER V. E. V. ST. , MOHAMMAD F. K.
Published: April 2008

The effects of N‐acetylcysteine (NAC) on the pharmacokinetic parameters of acetaminophen (AP) in adult female beagles were studied. Each of eight dogs received a single i.v. injection of 150 mg/kg of AP as a 5% solution in a vehicle of 40% aqueous propylene glycol at 0h. Each of four AP‐treated dogs (Group I) received an oral dose of 140 mg/kg NAC as a 20% aqueous solution at 0h, and 70 mg/kg at 30 min and 1h post‐AP administration. Four dogs (Group II) served as controls and received isotonic saline orally. Mild signs of AP toxicosis seen in both groups within 2‐3h of AP administration including depression, weakness, recumbency and methaemoglobinaemia. Relative to Group II, treatment with NAC (Group I) enhanced the elimination of AP from the body as indicated by the decreased plasma half‐life (t1/2=1.06h for Group I v. 1.78h for Group II) and a higher elimination rate constant (ß=0.67/h for Group I v. 0.40/h for Group II). Changes in the area under plasma concentration curve data (AUC=0.39 mg.h/ml for Group I v. 0.65 mg.h/ml for Group II) were associated with a 61% increase in total body clearance of AP in Group I. The apparent volume of drug distribution Vdarea was not affected.
Treatment of Moraxella bovis infections in calves using a long‐acting oxytetracycline formulation
Authors: GEORGE LISLE W. , SMITH J. A.
Published: April 2008

George, L.W. & Smith J.A. Treatment of Moraxella bovis infections in calves using a long‐acting oxytetracycline formulation. J. vet. Pharmacol. Therap. 8, 55–61.

Studies were undertaken to determine the effectiveness of an oxytetracycline HCl formulation for the prophylaxis and treatment of chronic Moraxella bovis ocular infections in calves. Two separate experiments were performed. For the first, calves were separated into two groups and the eyes were infected with M. bovis. The eyes of these calves were observed and cultured for 37 consecutive days. On the 37th and 40th day, each of the five calves were treated intramuscularly with the drug (20 mg/kg of body weight). The other five calves (second group) remained untreated as controls. The cultures from the five treated calves were negative after the first antibiotic administration and remained so for 14 days. M. bovis was isolated from each eye of the control calves at least once during that time. None of the antibiotic‐treated calves was completely resistant when reinfected with M. bovis. For the second experiment, calves were given a prophylactic administration of the formulation and were then infected with M. bovis 48 (n= 4 calves) or 72 (n= 4 calves) h later. These treatments resulted in a lower incidence of keratoconjunctivitis and a decreased duration of bacterial shedding, as compared to controls (n= 8 calves), but did not completely prevent the occurrence of disease or the establishment of ocular infections.

Lisle W. George, Department of Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
Clinical pharmacology of apramycin in calves
Authors: ZIV G. , BOR A. , SOBAGK S. , ELAD D. , NOUWS J. F. M.
Published: April 2008

Ziv, G., Bor, A., Sohack, S., Elad, D. & Nouws, J.F.M. Clinical pharmacology of apramycin in calves. J. vet. Pharmacol. Therap. 8, 95–104.

The minimal inhibitory concentrations (MIC) of apramycin, a unique aminocy‐clitol antibiotic, were compared with the MIC of dihydrostreplomycin and neomycin for 323 Salmonella, 178 Escherichia coli and twenty‐six Pasteurella multocida isolates recovered from newborn calves. Apramycin exhibited better in vitro anti‐bacterial activity than dihydrostreptomycin and neomycin; isolates of Salmonella group B and E. coli resistant to the latter were sensitive to apramycin.

The durations of free drug concentrations in the tissues after i.v. and i.m. injection were estimated from the serum drug level data, percent of serum protein binding, Vdss, 1/2ß and the MIC. Computations showed that apramycin should be administered i.m. at 20 mg/kg every 24 h in order to maintain in tissues potentially effective drug concentrations sufficient to inhibit 50% of the Salmonella, E. coli, and P. inullocida isolates, and at 12‐h intervals to inhibit 90% of the isolates.

G. Ziv, Ministry of Agriculture, Kimron Veterinary Institute, P.O. Box 12, Bet Dagan, Israel.
The effect of intermittent treatment with sulphadimidine on coccidiosis in preruminant calves
Authors: ĈELEDA L. , URBANOVÁ Z. , PAVLÁSEK I. , ĈERNÝ J. , RAŜKOVÁ H. , VANÊĈEK J. , KUBIĈEK A.
Published: April 2008

Ĉeleda, L., Urbanová, Z., Pavlásek, I., Ĉerný, J., Raŝkova, H., Vanêĉek, J. & Kubiĉek, A. The effect of intermittent treatment with sulphadimidine on coccidiosis in preruminant calves.J. vet. Pharmacol. Therap.8, 174–180.

Preruminant calves excreted coccidia oocysts in their faeces after 3 weeks of group housing. Two weeks of oral sulphadimidine (SDM) administration, 50mg/kg on the first day of treatment followed by daily administration of 37.5mg/kg, under the same housing conditions kept the faeces free of oocysts. Three weeks later, these calves excreted oocysts again. Repetition of the same treatment for 2 weeks controlled the infection again, but a second treatment for 5 days did not suffice. The repeated long treatment affected immunoglobulin levels adversely. SDM given repeatedly at a lower dose rate (30mg/kg) for 1‐week periods with medication‐free intervals of 1 week controlled the infection and no adverse effects were noted. In comparison with controls, weight gains were greater in treated calves.

L. Ĉeleda, Institute of Pharmacology, Albertov 4, 128 00 Prague 2, Czechoslovakia.
Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration
Authors: ORSINI J. A. , SOMA L. R. , ROURKE J. E. , PARK M.
Published: April 2008

Orsini, J.A., Soma, L.R., Rourke, J.E. & Park M. Pharmacokinetics of amikacin in the horse following intravenous and intræmuscular administration. J. vet. Pharmacol. Therap. 8, 194–201.

The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 ± 0.3, 61.2 ± 6.9 and 122.8 ± 7.4 (μg/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post‐injection and were 13.3 ± 1.6, 23.0 ± 0.6 and 29.8 ± 3.2 μg/ml, respectively. The t1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively. In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens. Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life‐threatening infections, dosing three times a day.

J. A. Orsini, University of Pennsylvania, School of Veterinary Medicine, New Bolton Center Campus, Kennett Square, PA 19348, U.S.A.
Disposition of sulfadimidine and its N4‐acetyl and hydroxy metabolites in horse plasma
Authors: NOUWS J. F. M. , VREE T. B. , BAAKMAN M. , DRIESSENS F. , SMULDERS A. , HOLTKAMP J.
Published: April 2008

Nouws, J.F.M., Vree, T.B., Baakman, M., Driessens, F., Smulders, A. & Holtkamp, J. Disposition of sulfadimidine and its N4‐acetyl and hydroxy metabolites in horse plasma. J. vet. Pharmacol. Therap. 8, 303–311.

The plasma disposition of sulfadimidine (SDM) and its metabolites N4‐acetylsulfadimidine (N4‐SDM), 6‐hydroxymethyl‐4‐methyl‐pyrimidine (SCH2OH) and 5‐hydroxy‐4,6‐dimethyl‐pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross‐over trials. The percentages of N4‐SDM (0.58‐0.90%), SOH (0.83‐6.75%) and SCH2OH (0.38‐0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half‐life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0, 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5–73.3% and 50.5–52.1%; SOH: 47.1–71.0% and 36.7–39.5%, and for N4‐SDM: 45.9–63.2% and 38.3–53.7%. The protein binding for SCH2

OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%.

Dr J. F. M. Nouws, RVV‐District 6, Wolfskuilseioeg 279, Nijmegen, Tlie Netherlands.
The influence of flumequine on the resistance of the coliform flora of chickens to the agent
Authors: HINTON M. , LINTON A. H.
Published: April 2008

Flumequine (1 g/1) was administered to healthy young chickens in the drinking water for 5 days. A transient increase in the incidence of resistance to flumequine (4 μg/ml) was recorded in faecal coliform isolates after administration. Cross‐resistance with nalidixic acid was demonstrated, but there was no evidence of cross‐resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, sulphadiazide, tetracycline and trimethoprim.
The effects of alpha2 adrenoceptor agonists on airway pressure in anaesthetized sheep
Authors: NOLAN A. , LIVINGSTON A. , WATERMAN A.
Published: April 2008

Xylazine and clonidine, given intravenously, cause an increase in airway pressure in the anaesthetized, ventilated sheep. This increase was dose dependent and was not mediated by histamine, nor was it blocked by the α1‐adrenoceptor antagonist prazosin. However, the increase was abolished by the α2‐adrenoceptor antagonist, idazoxan. When the α2‐adrenoceptor agonists were administered into the cerebrospinal fluid by injection into the cisterna magna there was no increase in airway pressure, although a similar dose given peripherally still produced an effect. These findings would indicate that the increase in airway pressure seen in these sheep, following administration of xylazine and clonidine, was mediated by peripherally located α2‐adrenoceptors.
Alteration in the arrhythmogenic dose of epinephrine (ADE) following xylazine administration to halothane‐anesthetized dogs
Authors: TRANQUILLI W.J. , THURMON J. C. , BENSON G.J. , DAVIS L. E.
Published: April 2008

The arrhythmogenic dose of epinephrine (ADE) was determined in six dogs during halothane (1.35%) anesthesia before and after xylazine administration (1.1 mg/kg, i.v. bolus; 1.1 mg/kg/hr, i.v. infusion). The arrhythmogenic dose was determined by constant infusion of freshly mixed epinephrine (100 μg/ml). The ADE was defined as the total dose of epinephrine which produced four or more intermittent or continuous premature ventricular contractions within a 15‐sec period. Total dose was calculated as a function of infusion rate and time to arrhythmia. Following xylazine administration, ADE significantly decreased from 6.28 ± 0.522 to 4.17 ± 0.679 μg/kg. At the end of i.v. xylazine bolus administration, heart rate significantly decreased (115 ± 4 to 99 ± 4.9 b.p.m.), and mean arterial pressure significantly increased (83 ± 4.0 to 122 ± 3.4 mm Hg). Heart rate measured immediately prior to epinephrine‐induced arrhythmia formation was significantly increased following xylazine administration (177 ± 8 vs 78 ± 3 b.p.m.). Mean arterial blood pressure was unchanged. Apparently, xylazine, a mixed a agonist, potentiated halothane‐induced myocardial sensitization to ventricular arrhythmogenesis and was associated with a significant increase in heart rate, but not blood pressure, during subsequent epinephrine infusions.
Radioimmunoassay of the anabolic agent zeranol. V. Residues of zeranol in the edible tissues, urine, faeces and bile of steers treated with Ralgro
Authors: DIXON S. N. , RUSSELL K. L. , HEITZMAN R.J. , MALLINSON C. B.
Published: April 2008

Dixon, S.N., Russell, K.L., Hekzman, RJ. & Mallinson, C.B. Radioimmunoassay of the anabolic agent zeranol. V. Residues of zeranol in the edible tissues, urine, faeces and bile of steers treated with Ralgro. J. vet. Pharmacol. Therap. 9, 353–358.

Two trials were conducted on steers implanted with zeranol (Ralgro) to determine the edible tissue residues and the secretion pattern in faeces, urine and bile of zeranol residues throughout and beyond the recommended withdrawal period (70 days) for this drug. In the first trial there was considerable variation in the zeranol residue concentration in all edible tissues, the highest concentrations found in the liver being significantly above the control values (P < 0.05). In the other tissues, only fat sampled 14 days after implanting was significantly above the control value (P < 0.05). The zeranol concentration in bile samples obtained at slaughter [70 days (18), 90 days (5) and 120 days (2)] were all higher than the apparent concentration in the bile of untreated steers. The mean concentration of zeranol in the faeces and urine varied from day to day and between animals sampled on the same day following implantation. The highest mean concentrations were observed during the first 40 days following implanting, declining steadily to approach the control values 70 days after implantation. The second trial using steers prepared with bile duct re‐entrant cannulae resulted in a similar pattern of zeranol excretion in bile, faeces and urine. The highest concentrations of zeranol were observed in bile and ranged from 24 to 34 μg/l; there was considerable variation between animals and within animals sampled on successive days. Although the concentration declined steadily, zeranol was still readily detectable 120 days after implanting. The residue data obtained in this study would suggest that although the most suitable biological samples for a monitoring programme would probably be bile and liver, it would be difficult to use residue data in these tissues to regulate the withdrawal period of zeranol.
Procainamide in the dog: antiarrhythmic plasma concentrations after intravenous administration
Authors: PAPICH MARK G. , DAVIS LLOYD E. , DAVIS CAROL A.
Published: April 2008

Papich, M.G., Davis, L.E. & Davis, C.A. Procainamide in the dog: antiarrhythmic plasma concentrations after intravenous administration.J, vet. Pharmacol. Therap.9, 359–369.

Procainamide hydrochloride was administered to ouabain‐intoxicated dogs to determine an antiarrhythmic plasma concentration of procainamide. Ventricular arrhythmias were produced in dogs following intravenous injections of ouabain. After a sustained ventricular tachycardia was achieved, procainamide was administered and plasma samples collected for assay. Plasma procainamide was assayed by fluorescence polarization immunoassay. Procainamide was administered at increasingly higher constant rate infusions in order to achieve intermittent, steady‐state plasma concentrations. Infusion rates were calculated on the basis of previous pharmacokinetic information.

All six dogs that received procainamide converted to a normal sinus cardiac rhythm after attaining a mean plasma concentration of 33.8 μg/ml with a range of 48.5 μg/ml—25.0 μg/ml. It was observed that the computer‐generated prediction of plasma concentrations based upon previous pharmacokinetic data produced an underestimate of the actual plasma concentrations. These data may suggest that plasma concentrations of procainamide for controlling some cardiac arrhythmias in dogs may be higher than plasma concentrations cited for human patients.
α1‐acid glycoprotein and serum binding of drugs in healthy and diseased dogs
Authors: BELPAIRE F. M. , RICK A. DE , DELLO C. , FRAEYMAN N. , BOGAERT M. G.
Published: April 2008

Belpaire, F.M., De Rick, A., Dello, C., Fraeyman, N. & Bogaert, M.G. apacid glycoprotein and serum binding of drugs in healthy and diseased dogs. J. vet. Pharmacol. Therap. 10, 43–48.

Inter‐individual variation in drug serum protein binding was studied in healthy dogs and in dogs with inflammatory diseases for lidocaine, oxprenolol and propranolol, which bind mainly to α1‐acid glycoprotein (α1‐AGP), and for diazepam, digitoxin and phenytoin, which bind mainly to albumin. For the drugs mostly bound to α1‐AGP, in both groups of dogs binding varied considerably, and it was markedly higher in dogs with inflammatory disease. For the other drugs, the variation in binding was smaller and did not differ between the two groups of dogs. In both groups of dogs, the α1‐AGP concentration varied widely; it was higher in the serum of the dogs with inflammation, while the concentration of albumin was lower in these animals. There was a significant negative correlation between percentage free lidocaine, oxprenolol or propranolol and α1‐AGP concentration, suggesting that the inter‐individual variation in binding of these drugs is due to the variation in α1‐AGP concentration. There was a marked intra‐individual variation in lidocaine binding and in serum α1‐AGP concentration, studied over a period of 3 weeks in healthy dogs; a significant negative correlation between percentage free lidocaine and α1‐AGP concentration was obtained.
Pharmacokinetics of oxfendazole in goats: a comparison with sheep
Authors: BOGAN J. , BENOIT E. , DELATOUR P.
Published: April 2008

Bogan, J., Benoit, E. & Delatour, P. Pharmacokinetics of oxfendazole in goats: a comparison with sheep. J. vet. Pharmacol. Therap. 10, 305–309.

In goats, there was a linear correlation of area under the plasma concentration–time curve (AUC) with dose in the range 0–20 mg/kg as single dosages of oxfendazole (OFZ). The bioavailability of OFZ after oral administration was lower in goats than in sheep. The repetition of three administrations at 24 h intervals produced significant increase in the AUC in comparison with a single administration equivalent to the total dosage (1 × 5.0 and 3 × 1.7 mg/kg). Infection with O. circumcincta produced a 33% decrease in the bioavailability of OFZ.
Colonic α2‐adrenoceptor‐mediated responses in the pony
Authors: ROGER T. , RUCKEBUSCH Y.
Published: April 2008

Roger, T. & Ruckebusch, Y. Colonic α2‐adrenoceptor‐mediated responses in the pony. J. vet. Pharmacol. Therap. 10, 310–318.

The motor responses of the caecum and colon to stimulation of α2‐adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra‐arterial infusion of a prostaglandin (PGF2α) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of α2‐agonists inhibited the spiking activity on the whole of the large intestine for 20–30 min (xylazine) or 2–3 h (detomidine). However, the detomidine‐induced inhibition was preceded by a short period of increased smooth muscle basal tone as indicated by strain‐gauge force transducer measurements. This pattern of activity was neither reversed nor prevented by the administration of tolazoline (10 μg/kg/min) intra‐arterially. In contrast, inhibition of the colonic phasic and tonic motor activity by α‐adrenoceptor stimulation was reversed competitively by tolazoline. The intra‐arterial infusion of prostaglandin F2α (10 μg/kg/min) induced prolonged and sustained spiking activity that might be related to signs of mild colic. Detomidine, and to a lesser extent xylazine, relaxed the whole of the large intestine and this was accompanied by alleviation of the signs of visceral pain.
Dose‐dependent plasma elimination of subcutaneously administered calcium heparin in horses
Authors: GERHARDS H. , KIETZMANN M.
Published: April 2008

Gerhards, H., & Kietzmann, M. Dose‐dependent plasma elimination of subcutaneously administered calcium heparin in horses.J. vet. Pharmacol. Therap.11, 77–83.

Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 ± 0.016 (mean ± SD) units of heparin/ml of plasma (U/ml) after 60 U/kg, 0.035 ± 0.025 U/ml after 80 U/kg, 0.023 ± 0.004 U/ml after 100 U/kg, 0.034 ±0.019 U/ml after 125 U/kg, and 0.053 ±0.019 U/ml after 150 U/kg. Data from groups given 60 and 100 U/kg could not be used for kinetic calculations. Elimination constant (1/h), elimination half‐life (h), and elimination time (h) calculated to reach base‐line values after 80 U/kg were 0.182 ± 0.041 1/h, 3.8 ± 0.9 h, and 9.7 + 2.2 h. After 125 U/kg, corresponding values were 0.211 ± 0.019 1/h, 3.3 ± 0.3 h, 13.4 ± 1.2 h, and after 150 U/kg 0.098 ± 0.015 1/h, 7.1 ± 1.1 h, and 20.6 ± 3.2 h. Calculated heparin concentrations 12 h after administration of 80, 125, and 150 U/kg were 0.011 ± 0.002, 0.010 ± 0.001, and 0.027 ± 0.004 U/ml. After seven successive injections of 150 U/kg at 12 h intervals in one horse, the elimination constant decreased from 0.23/h after the first to 0.08/h after the seventh injection, and the elimination time increased from 10 h to 40 h. Reducing the dosage from 150 U/kg initially to 125 U/kg for six successive injections reduced the prolonged elimination after repeated injections.