bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypnoanalgesia with R 8110/fentanyl in the dog: pharmacodynamic and pharmacokinetic interactions
Authors: MONBALIU J. , DEGRYSE A.‐D. , OOMS L. A. A. , DIJK. P. VAN , LAGERWEIJ. E. , MICHIELS M. , WOESTENBORGHS R. , HEYKANTS J.
Published: April 2008

Monbaliu, J., Degryse, A.‐D., Ooms, L.A.A., Van Dijk, P., Lagerweij, E., Michiels, M., Woestenborghs, R. & Heykants, J. Hypnoanalgesia with R 8110/ fentanyl in the dog: pharmacodynamic and pharmacokinetic interactions. J. vet. Pharmacol. Therap.11, 63–70.

The pharmacokinetics and clinical effects of the short‐acting hypnotic R 8110 and of the narcotic analgesic fentanyl were studied in the dog. The effects of separate intravenous (i.v.) injections of R 8110 (4 mg/kg) and fentanyl (0.015 mg/kg) and of concurrent i.v. injection of the two were studied. After administration of R 8110, induction of hypnosis occurred within 1 min, maximal depth of anaesthesia and satisfactory analgesia and muscle relaxation were obtained after 5 min. The effects had decreased within 15 min and full recovery occurred within 30 min. Fentanyl alone produced neither hypnosis nor muscle relaxation. When fentanyl and R 8110 were given simultaneously, the duration of hypnosis was doubled in comparison with R 8110 alone. Moreover, markedly improved and longer lasting analgesia and muscle relaxation were observed with the combination. When the drugs were injected together, the plasma concentrations of R 8110 were initially much higher than after separate injection of R 8110, but they became similar after 30 min. Although statistically non‐significant, fentanyl reduced the total plasma clearance of R 8110 (31.1 ± 6.9 MS. 21.9 ± 2.3 ml/kg/min) and decreased the volume of distribution (3.78 ± 1.83 vs. 2.23 ± 0.90 1/kg, P < 0.05). Fentanyl did not alter the elimination half‐life ofR8110. R8110 had no apparent influence on the pharmacokinetics of fentanyl.
Pharmacokinetics of ketamine HC1 and metabolite I in the cat: a comparison of i.v., i.m., and rectal administration
Authors: HANNA R. M. , BORCHARD R. E. , SCHMIDT S. L.
Published: April 2008

Hanna, R.M., Borchard, R.E. & Schmidt, S.L. Pharmacokinetics of ketamine HC1 and metabolite I in the cat: a comparison of i.v., i.m., and rectal administration. J. vet. Pharmacol. Therap. 11, 84–93.

Ketamine HC1 [2‐(o‐chlorophenyl)‐2‐(methylamino) cyclohexanone HC1] concentrations in whole blood were used to study the pharmacokinetics of i.v., i.m., and rectal administrations, at a dose of 25 mg/kg, in normal domestic cats. Absorption was rapid with both the i.m. and rectal routes. Systemic availability was 51% (SEM 10) for the i.m. dose and 43.5% (SEM 6.1) for the rectal dose. The first‐pass effect had a minimal influence on the metabolism of ketamine HC1 administered rectally. The elimination rate constant (β) of the drug was statistically similar in the i.v., i.m., and rectal groups, at a 95% level of significance (P < 0.05). At the dosage rates studied, ketamine HC1 produced an anesthetic effect in the cat following i.v., i.m. and rectal administration.
Effects of paracetamol and acetylsalicylic acid on the post‐operative course after experimental orthopaedic surgery in dogs
Authors: MBURU D. N. , MBUGUA S. W. , SKOGLUND L. A. , LOKKEN P.
Published: April 2008

Mburu, D.N., Mbugua, S.W., Skoglund, L. & Lökken, P. Effects of paracetamol and acetylsalicylic acid on the post‐operative course after experimental orthopaedic surgery in dogs. J. vet. Pharmacol. Therap.11, 163–171.

In placebo‐controlled cross‐over trials in dogs, two ‘identical’ operations were performed on the forelimbs of each animal with an interval of 28 days, to evaluate how daily doses of 1.5 g paracetamol, 1.5 g acetylsalicylic acid (ASA) and 0.5 g ASA might modulate an acute post‐operative inflammatory reaction. On the third post‐operative day the reductions in swelling compared with placebo averaged 33% with 1.5 g paracetamol (P = 0.02), 24% with 1.5 g ASA (P = 0.03) and 15% with 0.5 g ASA (P= 0.18); while the reductions in pain estimates averaged 47% with 1.5 g paracetamol (P= 0.01), 32% with 1.5 g ASA (P= 0.07) and 28% with 0.5 g ASA {P= 0.21). There were no clinical signs of adverse drug effects, such as vomiting, haematochezia, cyanosis or depression. The results disagree with the traditional view that paracetamol has little or no anti‐inflammatory effect, and demonstrate that paracetamol may reduce an acute inflammatory reaction, at least as efficiently as ASA. The potential proinflammatory effect of ASA in low doses is discussed. It is concluded that paracetamol appears to be a valuable drug against post‐operative or post‐traumatic sequelae in the veterinary as well as in the human clinic.
Pharmacokinetics of a long‐acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle
Authors: SANDERS P. , GUILLOT P. , MOUROT D.
Published: April 2008

Sanders, P., Guillot, P. & Mourot, D. Pharmacokinetics of a long‐acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle. J. vet. Pharmacol. Therap. 11, 183–190.

The pharmacokinetic properties of a long‐acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extra vascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration‐time graph was characteristic of a two‐compartment open model. Mean values were a half‐life of 4.1 h, a volume of distribution of 0.86 1/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10–15 Hg/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 μg/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.
Investigation of the effects of histamine inhalation on the tracheobronchial tree of calves by the forced oscillation technique
Authors: GUSTIN P. , DHEM A. R. , LEKEUX P. , LOMBA F. , LÁNDSÉR F.J. , WOESTIJNE K. P. VAN DE
Published: April 2008

Gustin, P., Dhem, A.R., Lekeux, P., Lomba, F., Lándsér, F.J. & Van de Woestijne, K.P. Investigation of the effects of histamine inhalation on the tracheobronchial tree of calves by the forced oscillation technique. J. vet. Pharmacol. Therap. 11, 374–380.

Effects of histamine inhalation were investigated with two different techniques in nine conscious, healthy calves. The oesophageal balloon technique was used to measure the dynamic respiratory compliance (Cdyn) and the pulmonary resistance (RL). The reactance (Xrs) and the resistance (Rrs) of the respiratory system were measured at high frequencies by the forced oscillation technique. These parameters were recorded before and after histamine inhalation. Three histamine dihydrochloride solution concentrations were used (16 mg/ml; 32 mg/ml; 64 mg/ml). Histamine inhalation induced a decrease in Cdyn and Xrs an increase in Rrs, RL and of the resonant frequency and a negative frequency dependence of Rrs. Some of these changes were satisfactorily correlated with the histamine solution concentrations. The resonant frequency was well correlated with Cdvn. It was concluded that histamine inhalation induces a decrease of the calibre of small and large airways and a non‐homogeneous behaviour of the pulmonary ventilation in awake calves. The forced oscillation technique can be used to perform an inhalation provocation test in unsedated animals.
Oral clindamycin disposition after single and multiple doses in normal cats
Authors: BROWN S. ANTHONY , DIERINGER T. M. , HUNTER R. P. , ZAYA M.J.
Published: April 2008

Eighteen normal cats were randomly allocated into three treatment groups and dosed with clindamycin aqueous solution for 10 days at a dosage rate of: (1) 5.5 mg/kg b.i.d.; (2) 11 mg/kg b.i.d.; or (3) 22 mg/kg once daily. Serum disposition of clindamycin was determined after the first and last dose of clindamycin was given, and was analyzed using model‐independent pharmacokinetics by both the trapezoidal rule method and the predictive equation method. Complete blood counts and clinical chemistries were determined before and after the study. The trapezoidal rule method produced similar mean results with much less variance than the predictive equation method. Mean residence time was longer (P < 0.05) after the high dose (393 ± 77 min) than after either the low or medium doses (276 ±51 and 274 ± 45 min, respectively). Oral volume of distribution (Vd(ss)/F) after the high dose (3.06 ± 0.921/kg) was larger (P < 0.05) than that after the low or medium doses (1.62 ± 0.30 and 1.76 ± 0.53 l/kg, respectively). Oral Vd(ss)/F was significantly smaller (P < 0.01) after the last dose than after the first dose when analyzed by treatment group. Significant (P < 0.01) decreases in the leuko‐gram and erythrogram were observed, due to the large amount of blood collected for drug analysis. No clinical signs of drug intoxication were observed, and no drug‐related necropsy findings were found.
In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens
Authors: PIJPERS A. , KLINGEREN B. VAN , SCHOEVERS E.J. , VERHEIJDEN J. H. M. , MIERT A. S.J. P. A. M. VAN
Published: April 2008

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline‐susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n= 17) 0.25–0.5 μg/ml; B. bronchiseptica (n= 20) 0.25–1.0 μg/ml; H. pleuropneumoniae (n= 20) 0.25–0.5 μg/ml; S. suis Type 2 (n= 20) 0.06–0.25 μg/ml. For 19 oxytetracycline‐resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 μg/ml for oxytetracycline to 0.5 μg/ml for minocycline. Strikingly, minocycline showed no cross‐resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampkillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lindomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.
Cardiovascular effects of detomidine, a new α2‐adrenoceptor agonist, in the conscious pony
Authors: SARAZAN R. D. , STARKE W. A. , KRAUSE G. F. , GARNER H. E.
Published: April 2008

The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post‐injection. The magnitude of the pressure change did not increase with detomidine doses greater than 20 μg/kg. There was a dose‐dependent effect on the duration of the hypertension. Bradycardia and A‐V blockade of similar magnitude followed the hypertension at all drug doses. Both drugs caused a negative inotropic effect on the heart at all doses. Minute work, a mechanical index of myocardial O2 demand, and coronary flow decreased to a similar extent following all drug treatments. With the exception of a greater hypertensive response, detomidine at the dosages studied, produced cardiovascular effects that were very similar to those of the recommended dosage of xylazine.
Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra)
Authors: GALEY F. D. , BEASLEY V. R. , SCHAEFFER D. J. , DAVIS L. E.
Published: April 2008

Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n= 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37°C. Six‐point Epi concentration‐response (C–R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each vessel using one of two concentrations of one of the three test drugs. Each drug and concentration combination was tested on a total of three arteries and three veins. Prazosin produced a concentration‐dependent shift of the Epi C–R curve to the right but the curve maintained the same maximum height and slope, which is consistent with competitive α1 adrenergic blockade. Isoxsuprine exhibited similar behavior, although the precise mechanism of action for isoxsuprine is unknown. Conversely, nifedipine did not shift the curve but did depress maximum contraction, suggesting a non‐competitive interaction consistent with its mechanism of calcium‐channel blockade.
Chemoprophylaxis and immunity to parasitic bronchitis in cattle — a field experiment comparing topical ivermectin and an oxfendazole intraruminal device
Authors: JACOBS D. E. , FOX M. T. , PILKINGTON J. G. , ROSS D. B. , RYAN W. G.
Published: April 2008

Seeder calves infected with Dictyocaulus viviparus were used to contaminate a Field divided into three similar paddocks. Twenty‐four autumn‐born calves were allocated to three matched groups; one group was given topical ivermectin treatments (0.5 mg/kg) at 3, 8 and 13 weeks after turnout (Day 0); each member of a second group was given an oxfendazole pulse‐release intraruminal device (OPRB) at turnout; while a third group was kept as untreated controls to monitor the natural epidemiological pattern of events. Severe pasteurella pneumonia exacerbated by lungworm infection occurred in the controls after Day 24. Two died and repeated doses of antibiotic and anthelmintic therapy were necessary to save the remainder. Clinical signs were much milder in the ivermectin and OPRB groups and resolved with only a single dose of antibiotic. The OPRB group excreted some lungworm larvae at this time, but none was detected in the faeces of the ivermectin group during the grazing season. At housing, five calves from each group and four lungworm‐naive calves were challenged with D. viviparus larvae. The infection became patent in all challenge‐control calves, but no larvae were passed by any of the trial animals. Post‐mortem worm‐counts revealed percentage takes for the challenge controls, trial controls, ivermectin and OPRB groups of 16.7, 0.01, 0.9 and 0.2, respectively. All trial groups had therefore developed a substantial immunity.
Superoxide production by stimulated equine polymorphonuclear leukocytes‐inhibition by anti‐inflammatory drugs
Authors: AUER D. E. , NG J. C. , SEAWRIGHT A. A.
Published: April 2008

Polymorphonuclear leukocytes (PMNLs) were isolated from an inflammatory exudate induced in the intercarpal joints of horses by an administration of carrageenin. Their superoxide production at rest and following stimulation with either serum‐treated zymosan (STZ) or phorbol myristate acetate (PMA) was measured by cytochrome‐c reduction. Stimulation of the cells increased the cytochrome‐c reduction 10‐15 times that of resting cells. The maxima were 20 nmol of reduced cytochrome‐c per 106 cells per ml at 120 min (STZ) and 35 nmol of reduced cytochrome‐c per 106 cells per ml at 60 min (PMA). The maximum inhibition of the cytochrome‐c reduction by superoxide dismutase (Paloseinr̀) was 83.6% (STZ stimulation) and 72.1% (PMA stimulation). The non‐steroidal anti‐inflammatory drugs, phenylbutazone, salicylic acid, aspirin, sodium salicylate in addition to D‐penicillamine and dimethylsulfoxide caused dose‐dependent inhibition of the cytochrome‐c reduction when the cells were stimulated by PMA. The maximum inhibitions were 64% and 36% for aspirin (10‐2 m), 32% and 17% for phenylbutazone (10‐3 m), 15% and 31% for dimethylsulfoxide (6.4 times 10‐1 M), 32% and 19% for salicylic acid (10‐2 M), 0% and 17% for sodium salicylate (10‐2 M) and 2.2% and 2.5% for D‐penicillamine (10‐4 M) when the cells were stimulated by STZ and PMA, respectively. The results indicate that equine PMNLs migrating from the vascular bed into the joint are a potential source of superoxide and that superoxide dismutase at achievable synovial fluid concentrations following intra‐articularly administered Paloseinr̀, and NSAIDs at concentrations above those achieved in plasma from therapeutic dose rates, may protect tissue from superoxide produced by equine PMNLs either stimulated by STZ or PMA.
Pharmacokinetic behaviour of netobimin and its metabolites in sheep
Authors: LANUSSE C. E. , PRICHARD R. K.
Published: April 2008

Lanusse, C.E. & Prichard, R.K. Pharmacokinetic behaviour of netobimin and its metabolites in sheep.J, vet. Pliarmacol. Therap.13, 170–178.

The pharmacokinetics and the profile of urine excretion of netobimin (NTB) and its metabolites were investigated after its intraruminal (i.r.) and subcutaneous (s.c.) administration to sheep at 20 mg/kg. Plasma and urine concentrations of NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) were measured serially over a 120‐h period by HPLC. NTB showed a similar pharmacokinetic profile in both treatments, being detected between 0.5 and 12 h post‐treatment, but the tmaxwas achieved significantly earlier (P < 0.05) after s.c. treatment. ABZ was detected in plasma only after i.r. treatment, resulting in a low area under the curve (AUC).The peak plasma concentration (Cmax) andAUCfor ABZSO and ABZSO2were significantly higher after i.r. administration of NTB. In both treatments, the ABZSO Cmaxwas reached earlier than the ABZSO2Cmax. The ratio ofAUCABZSO2:ABZSO was higher following s.c. administration (1.33) than following i.r. administration (0.35). The percentages of total dose excreted in the urine as NTB, ABZ, ABZSO and ABZSO2, were 17.05 (i.r.) and 8.16 (s.c). There was a less efficient conversion of NTB into ABZ metabolites after s.c. administration. The detection of ABZ in plasma and the high ABZSOAUCobtained after i.r. treatment may be of major importance for anthelmintic efficacy.

C. E. Lanusse, Institute of Parasitology, McGill University, Macdonald College, 21 III Lakeshore Road, Ste‐Anne de Bellevue, Quebec, Canada H9X ICO.
Drug plasma levels following administration of trimethoprim and sulphonamide combinations to broilers
Authors: LÖSCHER W. , FABBENDER C. P. , WEISSING M. , KIETZMANN M.
Published: April 2008

Löscher, W., Faßbender, C.P., Weissing, M. & Kietzmann, M. Drug plasma levels following administration of trimethoprim and sulphonamide combinations to broilers. J. vet. Pharmacol. Therap. 13, 309–319.

Trimethoprim (TMP) was administered in combination with either sulphadiazine or sulphadimidine to broilers, and plasma concentrations were determined simultaneously by newly developed thin‐layer and/or high‐performance liquidchromatographic procedures, which also allowed quantification of the N4‐acetyl metabolites of the sulphonamides. After i.v. injection of TMP (20 mg/kg body wt) and sulphadiazine (100 mg/kg body wt), both compounds were rapidly eliminated from plasma with half‐lives of 1 and 2.7 h, respectively. Apparent volumes of distribution (3.3 and 0.96 1/kg, respectively) indicated that the tissue distribution of TMP was more extensive than that of the sulphonamide. After oral administration of the same dosages, elimination appeared to be slower compared to the i.v. injection, but this was obviously related to delayed absorption. Bioavailability after oral administration was approximately 100% of sulphadiazine, but only about 60% for TMP. Oral dosing of TMP in combination with sulphadimidine yielded similar maximum plasma concentrations of both compounds to those obtained with the combination of TMP with sulphadiazine, but the plasma concentration decline of sulphadimidine appeared to be more rapid than that of sulphadiazine after oral administration. During prolonged administration of different dosages of TMP‐sulphadiazine combinations via drinking water, only low plasma concentrations were attained by the recommended dosage of the combination. Up to 10‐fold higher dosages were tolerated by the animals without side‐effects. In view of the fact that the sensitivity of bacterial strains to TMP‐sulphonamide combinations differs widely, the plasma concentrations determined in the present study during prolonged drinking‐water medication with different dosages of a TMP‐sulphadiazine combination can be used to select effective doses for treatment of different poultry diseases.

Prof. W. Löscher, Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bünteweg 17, D‐3000 Hannover 71, FRG
Effects of monensin on the bioavailability and elimination of selenium from blood in lambs
Authors: WANG J. H. , MIDDLETON D.J. , HUMPHREYS D.J.
Published: April 2008

Wang, J.H., Middleton, D.J. & Humphreys, D.J. Effects of monensin on the bioavailability and elimination of selenium from blood in lambs. J. vet. Pharmacol. Therap, 13, 378–385.

A bioavailability study was conducted in lambs following intravenous and oral administration of sodium selenite (0.4 mg selenium/kg body weight) with and without concurrent oral monensin. Two‐or three‐compartment open models with first‐order absorption after oral administration adequately described plasma selenium disposition irrespective of whether monensin was being administered. No significant differences were observed between groups of lambs receiving intravenous selenium with or without monensin with respect to distribution or elimination half‐lives of selenium, areas under the concentration‐time curve (AUC), volumes of distribution (Vd(ss), or clearances (CI). In lambs given selenium per os, no significant differences were observed with animals receiving monensin as well with respect to absorption and elimination half‐lives, Vd(ss), or the time at which peak selenium concentrations occurred (tmax). However, peak selenium levels (Cmax) and AUC values were significantly higher in the group given monensin. The bioavailability of selenium with and without monensin was estimated to be 60% and 43%, respectively.

Dr D. J. Middleton, Department of Veterinary Pathology, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts. AL9 7TA, UK.
Assessment of histamine, bradykinin, prostaglandins E1 and E2 and carrageenin as vascular permeability agents in the horse
Authors: AUER D. E. , NG J. C. , REILLY J. S. , SEAWRIGHT A. A.
Published: April 2008

The vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E1 and E2 was assessed. The test agents were injected intradermally into the shaved thoracic skin of horses and the vascular leakage estimated either semi‐quantitatively by recording the diameter of the lesions or by measuring the actual volume of extravasated plasma in microlitres using iodine‐125‐labelled human serum albumin (125I‐HSA) as a marker in the blood plasma. Using the latter method, the vascular leakage induced by carrageenin and the effect of coadministered prostaglandins E1 and E2 upon the vascular leakage of both histamine and bradykinin were also investigated. No obvious lesions resulted when serotonin (10‐2 mol/1) was injected but histamine and bradykinin produced circular lesions which increased in diameter for approximately 30 min. The size of the lesions and volume of extravasated plasma was dose dependent. On a molar basis, bradykinin (10‐6 mol/1, 10‐5 mol/1) was more potent than histamine but they were equipotent at 10‐4 mol/1. The size of the lesions induced by carrageenin were independent of their anatomical location on the thorax. Except for the second hour, the hourly volume of vascular leakage increased until the fifth hour when the experiment was concluded. The maximum vascular leakage resulting from the injection of prostaglandin E1 or E2 (1, 10, 100 or 1000 ng) was 7 μ but when co‐administered with bradykinin (10‐6 mol/1), the volume of leaked plasma increased from 29 to 78 μ. No synergy was observed when either prostaglandin was co‐administered with histamine (10‐5 mol/1).
Gentamicin pharmacokinetics in diabetic dogs
Authors: BROWN S. A. , NELSON R. W. , SCOTT‐MONCRIEFF C.
Published: April 2008

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, Five normal dogs, three dogs with alloxan‐induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using noncompartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 ± 2970 min, mean ± SD) was longer (P < 0.01) than in diabetic dogs (136 ± 164 min). In diabetic dogs, Cls was greater (3.01 ± 0.86 ml/min/kg) than in normal dogs (1.45 ± 0.11 ml/min/kg; P < 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 ± 0.508 1/kg) than in normal dogs (8.56 ± 4.48 1/kg; p,<0.01). Serum gentamicin concentrations were less than 0.020 μg/ml by 2 days in all of the diabetic dogs, but were 0.048 ± 0.018 (μg/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non‐rodent species.
The influence of chronic pain on the analgesic effects of the α2‐adrenoceptor agonist, xylazine, in sheep
Authors: LEY S. , WATERMAN A. , LIVINGSTON A.
Published: April 2008

A comparison of the analgesic potency of the α2‐adrenoceptor agonist, xylazine, in control healthy sheep and sheep suffering chronic pain from footrot, indicated that the analgesic effectiveness of xylazine was significantly reduced in the animals experiencing chronic pain. This was measured by recording the threshold to a mechanically applied pressure stimulus. Furthermore, when the condition was apparently resolved, by conventional treatment over a period of 2 to 3 weeks, the decreased analgesic effectiveness of the α2‐agonist was still apparent although the animals were clinically cured of the footrot.
Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine
Authors: MEVIUS D. J. , BREUKINK H. J. , van MIERT A. S. J. P. A. M. , KESSELS B. G. F. , JOBSE A. S. , SMIT J. A. H.
Published: April 2008

The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration‐time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three‐compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension it was best described by the one‐compartment open model with first‐order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)‐virus and 5 days later intrapulmonary administration of Pasteurella Iraemolylica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07± 0.04, 1.38 ± 0.36 and 0.50 ±0.11 1/kg, respectively) were smaller than those before infection, but the differences were not significant (P≤0.1). The intravenous AUC. was significantly increased (21.86 ± 3.51 to 33.85 ± 2.97 mg.h/I, P≤ 0.01) and the total body clearance (ClB) significantly decreased (0.24 ± 0.02 to 0.15 ± 0.01, P≤ 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 ± 14.3 to 59.7 ± 21.2%, P≤ 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7‐hydroxy‐flumequinerconjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection.
Eltenac, a new anti‐inflammatory and analgesic drug for horses: clinical aspects
Authors: PRÜGNER W. , HUBER R. , LÜHMANN R.
Published: April 2008

Two controlled studies to determine efficacy in the horse were performed with eltenac, a new injectable, non‐steroidal anti‐inflammatory drug (NSAID). Clinical trials were carried out with a dose rate of 1 mg/kg body weight in a randomized, placebo‐controlled, double‐blind design to assess therapeutic efficacy in acute inflammatory disorders and in animals with orthopaedic conditions. In a preliminary pharmacokinetic investigation in six horses mean elimination half‐life was 1.7 h after i.v. administration. In the first clinical study, analgesic activity on pain‐related lameness was determined in a total of 64 horses. Pain was assessed using a rating scale. Compared with the placebo treatment, eltenac produced significant pain relief after a single i.v. injection for a period of 24 h. In the second trial the anti‐oedematous effect was determined in post‐operative wound swelling following castration in two groups of 10 colts. After surgery, the horses received either an injection of 1 mg/kg eltenac or a placebo injection on three consecutive days. Swelling was assessed by measuring the diameter of the external preputial fold using two methods: callipers and a rating scale of 0 to 3. Additionally, photographs were taken on days 1, 2 and 4. Compared with the placebo treatment, eltenac inhibited pain and swelling significantly. The effect was maintained for up to 48 h after the last injection.
Pharmacokinetics of intravenous and oral methimazole following single‐and multiple‐dose administration in normal cats
Authors: TREPANIER L. A. , PETERSON M. E. , AUCOIN D. P.
Published: April 2008

The pharmacokinetics of methimazole (MMI) administered intravenously and orally were determined in six adult domestic shorthaired cats. There was no significant difference between mean serum MMI concentrations after oral and i.v. administration by 30 min post‐MMI administration, indicating relatively rapid and complete absorption of the drug. The bioavailability of MMI ranged from 27% to 100% (mean=81.1±11.4%). The mean serum elimination half‐life was 6.6±2.0 h, with a wide range of values (1.9h to 15.1h). After repeat i.v. administration of MMI following 2 weeks of oral administration of the drug, no significant difference was found between mean serum concentrations after single‐dose and multiple‐dose administration. No significant change in serum elimination half‐life or total body clearance was found after multiple‐dose administration of MMI. Two cats with the longest half‐lives (9.9h and 15.1h), however, did exhibit markedly shorter t1/2, values (3.5h and 3.3h, respectively) after multiple‐dose administration. Values for central and steady state volumes of distribution also decreased after multiple‐dose administration, possibly indicating saturation of thyroid uptake of MMI with chronic administration. These results indicate that MMI has good oral bioavailability and has a longer mean serum elimination half‐life than propylthiouracil, the other anti‐thyroid drug that has been evaluated in cats. Although no significant change in mean values occurred after multiple‐dose administration of MMI, drug‐induced acceleration of metabolism may occur in some cats after long‐term MMI administration.
Pharmacokinetics and milk residues of butorphanol in dairy cows after single intravenous administration
Authors: COURT M. H. , DODMAN N. H. , LEVINE H. D. , RICHEY M. T. , LEE J. W. , HUSTEAD D. R.
Published: April 2008

The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non‐lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 ± 1.145 (mean ± SD) I/kg, mean elimination half‐life was 82 min, and clearance was 34.6 ± 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmaco‐kinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant species.
Prescribing of veterinary and human preparations for animals in Norway. Was the preparation approved for the animal species for which it was prescribed?
Authors: GRAVE K. , BANGEN M. , ENGELSTAD M. , SØLI N. E.
Published: April 2008

The prescribing of drugs for case in veterinary medicine in Norway was investigated through a cross‐sectional survey. Of the 8741 prescriptions issued for animals included in this study 22% were for drug use in veterinarians' practices. Drugs from all but one therapeutic group were prescribed for use in animals. On average, 49% of the prescriptions were for vererinairy prepirations, 43% were for human preparations, and 8% were for formulations prepared by pharmacies. Of prescriptions for specific animal species, 27% of the preparations were not approved for the intended animal species. The corresponding figures for prescriptions of veterinary and human preparations were 7% and 41%, respectively. Of prescriptions for production animals 17% of the preparations were not approved for the intended animal species, and for pets this figure was 30%.
Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows
Authors: SANDERS P. , MOULIN G. , GUILLOT P. , DACORN M. , PERJANT P. , DELEPINE B. , GAUDICHE C. , MOUROT D.
Published: April 2008

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of niastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiraniycin at a dose of 30 000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significanlly longer (P < 0.01) in the milk (20.7 ± 2.7 h) than in plasma (4.0 ± 1.6 h). An average milk‐to‐plasma ratio of 36.5 ± 15 was calculated from the area concentration‐time curves. Severid pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction absorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for niaximal concentration in the milk. However, the two routes were bio‐equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland. These data indicate that spiramycin concentrations in milk were much higher than in plasma and were dependent on the route of administration. The two routes were bioequivalent for the length of time the milk concentrations exceeded the MIC, which is important for establishing dosage schedules.
Plasma concentrations of flunixin in the horse: its relationship to thromboxane B2 production
Authors: SOMA L. R. , UBOH C. E. , RUDY J. , FEGELY J.
Published: April 2008

The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2 (TxB2) concentrations were studied in sedentary and 2‐year‐old horses in training. The baseline TxB2 serum concentrations generated during clotting were 2.89 ± 81, 2.19 ± 0.25 and 0.88 ± 0.12 ng/ml for the 2‐year‐old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2 concentrations between older and younger horses (P < 0.005). Significant reduction in TxB2 production from baseline were noted at 1 (P < 0.01) and 4 h (P < 0.01) but not at 8 h after flunixin administration. The percent reduction in serum TxB2 concentration at 1 h after the administration of flunixin was 68.6 ± 7.8 and 45.2 ± 6.8 for the training and sedentary horses, respectively; the differences were significant (P < 0.04). Serum concentrations of TxB2 returned to baseline values by 12–16 h after flunixin administration. The results of this study indicate a difference in the TxB2 concentrations of older vs. younger horses and a difference in the suppression of TxB2 after the administration of flunixin in 2‐year‐old Thoroughbreds in training compared to sedentary horses. The results of this study suggest that the detection of low concentrations of flunixin in urine 24 h post‐administration may not represent pharmacologic effective concentrations of flunixin in plasma.
Temporal effects of inhaled histamine and methacholine aerosols on the pulmonary mechanics of Thoroughbred horses
Authors: GUTHRIE A. J. , BEADLE R. E. , BATEMAN R. D. , WHITE C. E.
Published: April 2008

This paper presents a method for on‐line determination of pulmonary mechanics in standing, non‐sedated horses during and following inhalation of aerosolized drug solutions. This method was used to evaluate the temporal effects of inhaled histamine and methacholine aerosols on pulmonary mechanics in 18 Thoroughbred horses. The following were concluded from this study. The extremely large between‐breath variation, for all variables used to evaluate pulmonary mechanics in the horse, limits the usefulness of these variables for modeling the non‐specific pulmonary responses to inhaled stimulants on a breath‐by‐breath basis. Following the implementation of averaging techniques to control the variation of these response variables, respiratory rate appears to be affected most predictably by inhalation of non‐specific bronchoconstrictors. In the 18 subjects studied, the response of respiratory rate to inhaled histamine and methacholine aerosols was well described by a complex function consisting of exponential treatment and post‐treatment phases in 10 and six of the subjects, respectively. Large intra‐individual variation of the non‐specific response to these. stimulants in repeated studies of some subjects, suggests that differences in responses on a particular day may be due to inter‐day variations in minute ventilation or baseline airway caliber.
The pharmacokinetics of flunixin meglumine in the sheep
Authors: WELSH E. M. , McKELLAR Q. A. , NOLAN A. M.
Published: April 2008

Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma‐ flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half‐life (t½π= 2.3 min), a slow body clearance rate (Clb= 0.6 ml/kg/min) and an elimination half‐life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t½π= 2.7 min, has a slow body clearance rate (C/b = 0.7 mk/lg/min) and an elimination half‐life of 205 min.

Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration (Cmax) of ≫5.9 μg/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg‐2.2 mg/kg when administered by the intramuscular route.
Circulatory and respiratory effects of the combination medetomidine‐ketamine in beagles
Authors: SERTEYN D. , COPPENS P. , JONES R. , VERSTEGEN J. , PHILIPPART C. , LAMY M.
Published: April 2008

The cardiovascular and respiratory parameters of eight laboratory beagles were measured before and after the simultaneous injection of medetomidine (40 /igl kg bw) and ketamine (5 mg/bg bw). This combination produced a significant alteration in cardiovascular function. The heart rate, the stroke volume and cardiac output decreased while the systemic vascular resistance increased. These effects were attributed principally to the a2 agonist compound combined with the moderate stimulatory effect of ketamine. The respiratory parameters were little affected by this protocol.
Comparative pharmacokinetic disposition of closantel in sheep and goats
Authors: HENNESSY D. R. , SANGSTER N. C. , STEEL J. W. , COLLINS G. H.
Published: April 2008

The pharmacokinetic disposition of closantel was examined following intraruminal (i.r.) or intramuscular (i.m.) administration to adult Merino sheep and to adult and 3‐month‐old, suckling Angora goats. In adult goats the maximum concentration (Cmax) and area under the plasma concentration with time curve (AUC) following 3.75, 7.5 and 15.0 mg closantel/kg given i.r. increased with dose however the time of Cmax (rmax= 2.6d) in plasma was unaffected by dose rate. The elimination phase (K10) of closantel was monoexponential with a half‐life (t½) of 4.7d again unaffected by dose rate. Apart from a more rapid absorption phase and earlier Tmax following 3.75 mg closantel/kg i.m., pharmacokinetic behaviour was similar to that following i.r. administration at 3.75 or 7.5 mg/kg. Although absorption rate was more rapid in kids after i.r. administration at 7.5 mg/kg, pharmacokinetic disposition of closantel was otherwise similar to that in adult goats. No closantel was detected in milk of treated does or in the plasma of their kids. I.R. closantel at 7.5 mg/kg was more slowly absorbed in goats than in sheep but Cmax was similar in both species. However, K10t½ was significantly shorter in goats (4d) than in sheep (14d). Faster elimination resulted in an almost three‐fold lowering of AUC in goats and could dramatically reduce the sustained action of closantel in this species compared with sheep.
The influence of Ostertagia circumcincta and Trichostrongylus colubriformis infections on the pharmacokinetics of febantel in lambs
Authors: DEBACKERE M. , LANDUYT J. , VERCRUYSSE J. , McKELLAR Q.
Published: April 2008

Plasma concentrations of febantel and its major metabolites fenbendazole, oxfendazole and oxfendazole sulphone were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 50 000 L3 larvae of Ostertagia circumcincta or Trichostrongylus colubriformis. The febantel concentrations were always very low and only in a few samples higher than the detection limit. The mean decrease in AUC for the three metabolites for the infected sheep in comparison to the parasite naive sheep was 13.9%± 4.1% (mean± SEM) and 23.7%± 5.3% in the 0. circumcincta infected and the T. colubriformis infected lambs respectively. This reduction was only significant for the T. colubriformis infected group.

In order to determine a more complete pharmacokinetic profile, febantel was injected intravenously at a dose of 2.5 mg/kg in a further study.
Regulation of uterine estrogen receptors (ER) by beta‐adrenergic stimulation in immature rats
Authors: RE G. , BADINO P. , DACASTO M. , CARLO F. DI , GIRARDI C.
Published: April 2008

The effects of a 3‐day intramuscular (i.m.) administration of clenbuterol (25 μ.g/ Kg), propranolol (12 mg/kg), clenbuterol (25 μg/kg) plus propranolol (12 mg/ Kg) and estradiol (0.5 μg) upon the female reproductive system were investigated in immature Sprague‐Dawley rats. Clenbuterol and estradiol treatments induced a significant increase in uterus weight and in relative uterus weight, whereas in the groups treated with propranolol and clenbuterol plus propranolol no differences were detected versus controls. The uterine estrogen receptor levels were significantly increased by clenbuterol administration. In the rats dosed with propranolol and clenbuterol plus propranolol, no modifications occurred in estrogen receptor concentrations when compared with control values. Uterine progesterone receptors were never significantly affected by any of the considered treatments. Data obtained indicate that clenbuterol treatment induces an increase in uterus weight and in estrogen receptor levels and that these effects are regulated by acute beta‐adrenergic stimulation, as the contemporaneous administration of high doses of a beta‐blocker inhibit such effects.
Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse
Authors: KOLLIAS‐BAKER C. A. , COURT M. H. , WILLIAMS L. L.
Published: April 2008

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin‐to‐floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin‐to‐floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.

The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A‐V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin‐to‐floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.