bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular and respiratory effects of acetylpromazine and xylazine on halothaneanesthetized horses
Authors: STEFFEY E. P. , KELLY A. B. , FARVER T. B. , WOLINER M. J.
Published: April 2008

Steffey, E.P., Kelly, A.B., Farver, T.B. & Woliner, M.J. Cardiovascular and respiratory effects of acetylpromazine and xylazine on halothane‐anesthetized horses. J. vet. Pharmacol. Therap. 8, 290–302.

Circulatory and respiratory effects of intravenously administered acetylpromazine (0.033 and 0.067 mg/kg) and xylazine (0.5 and 1.0 mg/kg) were studied in drug cross‐over fashion in eight laterally recumbent horses anesthetized only with halothane (1.06%, end‐tidal) in O2. Both doses of acetylpromazine caused a significant and sustained elevation in cardiac output via a rise in stroke volume. Xylazine produced an initial significant fall in cardiac output followed by a return to control levels. Halothane anesthesia did not prevent xylazine‐related atrioventricular conduction block. All treatments caused a similar significant fall in arterial blood pressure (acetylpromazine, total peripheral resistance‐related; xylazine, cardiac output‐related). PaCO2 significantly increased after all treatments. PaCC2 decreased significantly only following xylazine treatment. One horse (not included in the tabulation) developed ventricular fibrillation and died 15 min after receiving its first injection (0.5 mg/kg) of xylazine.

Dr E. P. Steffey, Department of Surgery, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
Ibuprofen prevents Pasteurella hemolytica endotoxin‐induced changes in plasma prostanoids and serotonin, and fever in sheep
Authors: EMAU P. , GIRI S. N. , BRUSS M. L. , ZIA SHAHEEN
Published: April 2008

Intravenous infusion of Pasteurella hemolytica endotoxin caused marked increases in the plasma levels of thromboxane B2 (TxB2), prostaglandins (PG) and serotonin in sheep. The control values for TxB2, 6‐keto‐PGF1a, PGF2a, and serotonin before endotoxin infusion averaged 283 ± 53 (standard error of mean), 281 ± 14 and 199 ± 27 pg/ml and 57 ± 3 ng/ml, respectively. At 50 min during endotoxin infusion, these values were increased to their maximum of 376, 339, 325 and 202% of control, respectively. Body temperature increased from the control value of 39.5 ± 0.1åC to a maximum of 41.5 ± 0.1åC at 200‐300 min of infusion. In the second part of this study, we have examined the effects of ibuprofen on endotoxin‐induced increases in plasma PG, TxB2, and serotonin levels and body temperature. The control values for TxB2, 6‐keto‐PGF1a, PGF2a, and temperature prior to ibuprofen and endotoxin infusion averaged 238 ± 35, 335 ± 44 and 248 ± 28 pg/ml, 65 ± 3 ng/ml and 40.1 ± 0.2åC, respectively. A loading dose (15 mg/kg) of ibuprofen was followed by infusion of endotoxin (12 μg/kg) and ibuprofen (43.3 mg/kg) over 500 min. Plasma levels of 6‐keto‐PGF1a and serotonin increased only to 131 and 149% of control at 50 min of infusion, and levels of PGF2a and TxB2 decreased to 50 and 80% of control at 100 and 150 min of infusion, respectively. Temperature remained unchanged. Ibuprofen effectively suppressed endotoxin‐induced increases in the plasma levels of TxB2, 6‐keto‐PGF1a, PGF2a, and serotonin and body temperature. It was concluded from the present study that nonsteroidal anti‐inflammatory drugs as an adjunct to antibiotic therapy might have a rational basis in treatment of endotoxin toxicity.
Radioimmunoassay of the anabolic agent zeranol. IV. The determination of zeranol concentrations in the edible tissues of cattle implanted with zeranol (Ralgro)
Authors: DIXON S. N. , RUSSELL K. L.
Published: April 2008

Rapid solvent extraction combined with a radioimmunoassay using a nionoclonal antibody raised against a derivative of zeranol has been used to measure the residues of the anabolic agent zeranol in the edible tissues (muscle, liver, kidney and fat) of cattle treated with Ralgro.

Calibration curves, both with and without, tissue extracts exhibit good parallelism. Regression analysis for the extraction of‐ zeranol from tissues dosed with standard amounts of zeranol have correlation coefficients of 0.979, 0.99 1, 0.986 and 0.985 for muscle, liver, kidney and fat, respectively.

The limits of decision defined as the mean value + 3 SD for the concentrations apparently observed (noise) in tissues from animals not treated with Kalgro were 278, 121, 373 and 110 ng/kg for muscle, fat, liver and kidney, respectively. In the tissues of 4 cows implanted with Ralgro (36 mg), and sampled 70 clays after iniplanting, the highest concentration of zeranol in each tissue was 232 ng/kg (muscle), 391 ng/kg (liver), 287 nglkg (kidney) and 293 nglkg (fat), and residues were detected in all samples of fat (4), 3 kidney samples and I liver sample.
Effect of ingesta on systemic availability of penicillins administered orally in dogs
Authors: WATSON A. D.J. , EMSLIE D. R. , MARTIN I. C. A. , EGERTON J. R.
Published: April 2008

Six penicillin preparations were administered to six dogs of various types, both when the dogs were fasted and when fed a standard meal immediately before dosing. The preparations used were: amoxycillin tablets and drops, ampicillin tablets, penicillin V tablets, phenethicillin tablets and cloxacillin capsules. A Latin square design was employed with ampicillin and the two amoxycillin preparations, while three separate cross‐over studies were done with penicillin V, phenethicillin and cloxacillin. Dose rates used were 50 mg/kg for cloxacillin, and 10 mg/kg for the others. A microbiological method was used to assay penicillin in blood samples taken at intervals after dosing. Values for peak plasma drug concentration (Cmax), the time at which it occurred (Tmax), and area under the curve (AUC) were obtained for each curve of drug concentration plotted against time. In fasted dogs, ampicillin showed poorer systemic availability than did amoxycillin, with Cmax and AUC values of less than half those of amoxycillin. The solid and liquid preparations of amoxycillin had similar bioavailability. Ingesta adversely affected the systemic availability of antibiotic from all preparations tested. With ampicillin and both amoxycillin preparations, there were reduced Cmax and AUC and prolonged Tmax, indicating slowed and diminished absorption. Feeding did not alter Tmax with the other drugs, but reduced the Cmax of penicillin V, phenethicillin and cloxacillin and the AUC of cloxacillin. It is suggested that, if minimal impairment of bioavailability by ingesta is desired, then the penicillins commonly administered by mouth (amoxycillin, ampicillin, pencillin V, phenethicillin, cloxacillin) should be given to dogs that are fasting.
Investigation into the inhibitory effect of flurofamide on animal ureaplasmas and its use in the treatment of ureaplasma‐infected sheep
Authors: BALL H.J. , McCAUGHEY W.J.
Published: April 2008

In vitro tests with the urease inhibitor flurofamide demonstrated that the final inhibitory concentration of 0.5‐4 μM on the growth of nine ureaplasma strains was largely ureaplasmastatic, requiring prolonged incubation to have a ureaplas‐macidal effect. Intramuscular injection of flurofamide successfully eliminated genital infections of ureaplasma in sheep only when the treatment was repeated on two consecutive days. A dose rate of 5–20 mg/kg body weight eliminated the organism from naturally infected sheep, but 15–25 mg/kg body weight was required to eliminate the infection from eleven of fourteen experimentally, newly infected sheep. Administration of the flurofamide orally in the drinking water failed to eliminate ureaplasmas from any of twenty newly infected sheep.
Pharmacokinetics of trimethoprim/sulfadiazine in neonatal calves: influence of synovitis
Authors: SHOAF S. E. , SCHWARK W. S. , GUARD C. L. , SCHWARTSMAN R. V.
Published: April 2008

Shoaf, S.E., Schwark, W.S., Guard, C.L. & Schwartsman, R.V. Pharmacokinetics of trimethoprim/sulfadiazine in neonatal calves: influence of synovitis. J. vet. Pharmacol. Therap. 9, 446–454, 1986.

The effect of synovitis on the distribution of antibacterial drugs into the joint space was studied in 1‐week‐old calves. Sodium urate crystals were used to induce inflammation in the tibio‐tarsal joint of calves and the antibacterial drug combination, trimethoprim/sulfadiazine (Tribrissen®), 30 mg/kg, was administered intravenously 3 h after synovitis was induced. The degree of synovitis was monitored by serial WBC counts in synovial fluid. Trimethoprim (TMP) and sulfadiazine (SDZ) concentrations in serum and synovial fluid were measured and pharmacokinetic parameters were calculated. The results indicated that inflammation had no effect upon the concentrations of TMP/SDZ that reach the joint and that synovial fluid and blood are both representative of the central compartment as shown by the non‐significant differences in selected pharmacokinetic parameters for TMP and SDZ in these two body fluids. The distribution and elimination of TMP and SDZ in serum were described by a two‐compartment model.
Pharmacological modulation of postprandial colonic motor activity in the pony
Authors: ROGER T. , RUCKEBUSCH Y.
Published: April 2008

Roger, T. & Ruckebusch, Y. Pharmacological modulation of postprandial colonic motor activity in the pony. J. vet. Pharmacol. Therap. 10, 273–282.

The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 μg/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10–15 min. In contrast, the intra‐arterial infusion of PGF2a (3 μg/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre‐treatment prevented the effects of postprandial, cholinergic and PGF2a stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2a excitatory effects.
A pharmacokinetic study of phenobarbital in mature horses after oral dosing
Authors: RAVIS W. R. , DURAN S. H. , PEDERSOLI W. M. , SCHUMACHER J.
Published: April 2008

Ravis, W.R., Duran, S.H., Pedersoli, W.M. & Schumacher, J. A pharmacokinetic study of phenobarbital in mature horses after oral dosing. J. vet. Pharmacol. Therap.10, 283–289.

The pharmacokinetics of phenobarbital were determined in six mature horses after a single oral dose. Horses were administered a 5.5 mg/kg of body weight oral dose of phenobarbital tablets. Based on the combined evaluation of i.v. and oral results, phenobarbital displayed two‐compartment pharmacokinetics in the horse with a terminal half‐life of 19.0 ± 4.4 (mean ± SD) h. This half‐life is considerably shorter than those reported for dogs and humans. The steady‐state volume of distribution (Vdss/F) and the total body clearance (Cl1/F) of phenobarbital were 0.753 ± 0.115 1/kg and 27.9 ± 9.2 ml/h/kg, respectively. The average extent of oral absorption was 101% with a range of 76 to 124% among the six horses. Examination of the absorption kinetics demonstrated a biphasic absorption process in four horses with a rapid absorption followed by a slower absorption phase. The mean residence time (MRT) was 36.9 ± 4.1 h and the mean residence time for oral absorption (MRTabs) was 11.3 h. Based on the results of the present study, an oral dosing regimen of 11 mg/kg of body weight every 24 h can be recommended.
The effect of age and diet on sulfadiazine/trimethoprim disposition following oral and subcutaneous administration to calves
Authors: SHOAF S. E. , SCHWARK W. S. , GUARD C. L.
Published: April 2008

Shoaf, S.E., Schwark, W.S. & Guard, C.L. The effect of age and diet on sulfadiazine/trimethoprim disposition following oral and subcutaneous administration to calves. J. vet. Pharmacol. Therap. 10, 331–345.

Thirty milligrams per kilogram of sulfadiazine/trimethoprim (SDZ/TMP, Trib‐rissen®) was given orally and subcutaneously (s.c.) to two groups of male, Hol‐stein calves. One group was fed milk‐replacer throughout the 13‐week period of the study while the second group was weaned onto a chopped grain‐fiber mixture when 5 weeks old. Serum and urine were assayed for concentrations of unchanged drug. Trimethoprim bioavailability, following oral administration at 1, 6 and 12 weeks of age, is higher in milk‐fed calves (non‐ruminants) than in grain‐fiber‐fed calves (ruminants); bioavailability decreases with increasing age in both groups of calves. Serum concentrations above 0.1 μg/ml (the level of sensitivity of the assay) could not be obtained in ruminating calves. The rate of SDZ absorption following oral administration, as determined by the Wagner‐Nelson method, was very slow in all the calves in this study with average half‐life values ranging from 8.2–12.67 h; absorption was slightly faster in ruminating calves. Absorption of SDZ is rate‐limiting and determines the biological half‐life of the drug; SDZ serum concentrations above 2 (μg/ml were maintained in all calves for at least 24 h. Following s.c. administration of Tribrissen®to 7‐and 13‐week‐old calves, urinary excretion patterns indicated that TMP was slowly released from the injection site; serum concentrations were below 0.1 μg/ml. In contrast, absorption of SDZ was very rapid; values for tmax were 1.5–1.8 h. The pharmacokinetic parameters for SDZ were calculated according to a one‐compartment open model; neither diet nor age had a significant effect on SDZ disposition following s.c. injection. Subcutaneous administration of 30 mg/kg Tribrissen®, b.i.d., may be the best therapeutic regimen; even though measure‐able concentrations of TMP cannot be achieved in the serum following a single s.c. dose, TMP concentrations should accumulate and, because of its sustained release, provide almost continual potentiation of SDZ.
Pharmacokinetics of dantrolene sodium in horses
Authors: COURT M. H. , ENGELKING L. R. , DODMAN N. H. , ANWER M. S. , SEELER D. C. , CLARK M.
Published: April 2008

The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half‐life of 129 ± 8 (SEM) min and a whole body clearance of 4.16 ± 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within 1.5 h, but was incompletely absorbed, with a bioavailability of 39 ± 10%. Small amounts of intact drug were recovered in urine and bile. Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range.
Comparison of the effects of etomidate and its fluoro analogue, R 8110, on plasma Cortisol, 11β‐deoxycortisol, 17α‐hydroxyprogesterone and testosterone concentrations in dogs
Authors: COSTER R. DE , DEGRYSE A.‐D. A. Y. , DIJK P. VAN , OOMS L. A. A. , LAGERWEIJ E.
Published: April 2008

R 8110, an imidazole derivative, was shown to be clinically superior to etomidate for induction and maintenance of anaesthesia in dogs. The present study compared the effects of intravenous (i.v.) R 8110, etomidate and Ringer solution on Cortisol biosynthesis by the adrenal gland in seven male labradors. A tetracosactide challenge was carried out 30 min after the i.v. injection of 3 mg/kg of both drugs and after i.v. Ringer solution (1 ml/kg). Etomidate and R 8110 both suppresed the Cortisol response to tetracosactide almost completely and increased the plasma 11β‐deoxycortisol levels more than 20 fold. Maximal 11β‐deoxycortisol values were reached 120 min after R 8110, and not less than 300 min after etomidate. Plasma 17α‐hydroxyprogesterone and testosterone concentrations did not differ between placebo and R 8110 treatment, but they decreased after etomidate. These results indicate that the effects of R 8110 on steroid biosynthesis in dogs are less pronounced than those of etomidate and are largely limited to a temporary inhibition of the 11β‐hydroxylase in the adrenal gland.
Florfenicol in non‐lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils
Authors: BRETZLAFF K. N. , NEFF‐DAVIS C. A. , OTT R. S. , KORITZ G. D. , GUSTAFSSON B. K. , DAVIS L. E.
Published: April 2008

Serial blood samples were collected and plasma concentrations of florfenicol (FLO) were measured following the administration of an intravenous bolus of 50 mg/kg FLO to five healthy non‐lactating dairy cows. A triexponential equation provided the best fit of the data for four of the five cows. The mean value for 8 corresponded to a half‐life of 3.2 h. The mean apparent volume of distribution was 0.67 1/kg, and the mean body clearance was 0.15 1/kg/h. The extent of binding of FLO to bovine plasma proteins was determined in vitro at concentrations of 5 μg/ml and 50 4mUg/ml by equilibrium dialysis and ultrafiltration. The drug was 18% and 19% bound by equilibrium dialysis, and 23% and 19% bound by ultrafiltration, at 5 μg/ml and 50 μg/ml, respectively. Phagocytosis of 32phosphorus‐labelled Staphylococcus aureus by bovine blood neutrophils was compared in vitro between neutrophils incubated in phosphate‐buffered saline alone or in combination with 5, 125, or 1000 μg/ml chloramphenicol or FLO. There was no significant effect of chloramphenicol at any concentration. Florfenicol significantly inhibited phagocytosis at all concentrations, but the percentage inhibition was small. The clinical significance, if any, of this effect of FLO remains to be demonstrated.
Effect of some vehicles used in intramammary mastitis preparations on inflammation indicators in milk
Authors: PYÖRÄLÄ S.
Published: April 2008

The irritant effect of some vehicles used in intramammary mastitis preparations was assessed by indirect mastitis indicators in milk. Mineral oil, soybean oil, peanut oil, a combination of aluminium monostearate, stearic acid and mineral oil as well as isotonic saline were infused intracisternally in cows during mid‐lactation. These vehicles induced a selective increase in the number of somatic cells without any notable effects on the permeability marker antitrypsin or the lysosomal enzyme N‐acetyl‐β‐D‐glucosaminidase (NAGase).
Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs
Authors: LABER G.
Published: April 2008

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap.11, 45–49.

Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax= 0.61 ± 0.15 μg/ml, a Tmax= 6 h and a t½= 4.7 ± 1.4 h. Tiamulin showed dose‐dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax= 1.55 ± 0.11 μg/ml, Tmax= 8 h and 1max= 4.28 ± 0.18 h were obtained. For the higher dose Cmax= 3.14 ± 0.04 μg/ml, Tmax= 8 h and t½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.
The oxidative metabolism of fenbendazole: a comparative study
Authors: SHORT C. R. , FLORY W. , HSIEH L. C. , BARKER S. A.
Published: April 2008

Short, C.R., Flory, W., Hsieh, L.C. & Barker, S.A. The oxidative metabolism of fenbendazole: a comparative study. J, vet. Pharmacol. Therap. 11, 50–55.

The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ‐SO), and p‐hydroxyfenbendazole (FBZ‐OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ‐NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ‐S02), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ‐OH and FBZ‐SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25oC and 37oC incubation temperatures. The formation of the sulfone metabolite (FBZ‐SO2), however, was practically nonexistent in catfish.
Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats
Authors: KNOPPERT N. W. , NIJMEIJER S. M. , DUIN C. T. M. VAN , KORSTANJE C. , GOGH H. VAN , MIERT A. S.J. P. A. M. VAN
Published: April 2008

Knoppert, N.W., Nijmeijer, S.M., van Duin, C.T.M., Korstanje, C., van Gogh, H. and van Miert, A.S.J.P.A.M. Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats. J. vet. Pharmacol. Therap.11, 135—144.

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick‐borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (w = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration—time curves for both drugs followed first‐order two‐compartment decay. For TMP, mean t½β± SEM (h) was 0.84 ± 0.06 (i.v. control) and 0.90 ± 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 ± 0.31 (i.v. control) and 10.28 ± 0.67 (i.v. infected) were obtained (P < 0.05). Mean Vdp± SEM values (1/kg) were 3.84 ± 0.27 (i.v. control) and 4.07 ± 0.85 (i.v. infected) for TMP (NS) and 7.02 ± 0.63 vs 9.29 ± 0.21 (P < 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P < 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 ± 0.06 (Xg/ml and 0.85 ± 0.17 (ig/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 ± 0.01 (ig/ml and the maximum was reached after 1.2 ± 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 ± 0.02 μg/ml with Tmax of 22.5 ± 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.
The pharmacodynamics of ivermectin in sheep and cattle
Authors: BOGAN THE LATE'J. A. , McKELLAR Q. A.
Published: April 2008

Bogan, J.A. (deceased) & McKellar, Q.A. The pharmacodynamics of ivermectin in sheep and cattle. J. vet. Pharmacol. Therap. 11, 260–268.

The concentrations of ivermectin in the gastrointestinal tract of sheep and cattle were determined after subcutaneous administration of ivermectin. Ivermectin was not detected (limit of detection 1 ng/ml) in abomasal and ruminal fluids either after a normal therapeutic dose of 200 μg/kg or even at an increased dose of 2000 μg/kg. It was also not detected in abomasal and ruminal fluids of a sheep infected with the abomasal parasite Osterlagia circumcincta. However, ivermectin was detectable at similar concentrations in abomasal mucus and in small intestinal mucus. Excretion of ivermectin was high in bile but the concentrations in small intestinal mucus, distal and proximal to the bile duct opening, were similar. It is hypothesized that the low efficacy of ivermectin against small intestinal nematodes compared with abomasal nematodes is not due to differences in ivermectin concentrations in the predilection sites but is probably due to tachyphylaxis in the nematodes allowing the small intestinal nematodes to re‐establish before they have left their predilection site. Ivermectin was excreted in the milk of ewes at concentrations similar to those in plasma. Lambs suckling ivermectin‐treated ewes received about 4% of a normal therapeutic dose (200 μg/kg) via the milk.
Actions of the novel gastrointestinal pro kinetic agent cisapride on equine bowel motility
Authors: KING J. N. , GERRING E. L.
Published: April 2008

King, J.N. & Gerring, E.L. Actions of the novel gastrointestinal prokinetic agent cisapride on equine bowel motility. J. vet. Pharmacol. Therap. 11, 313–321.

The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60‐min periods at 0.05 mg/kg (n= 4), 0.1 mg/kg (n= 5) and 0.25 mg/kg (n= 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and amplitude of contractions and a decrease in the number of regular (phase III) activity fronts. There was a decrease in the number of phase III fronts that spread distally from the jejunum to the ileum. The phase II activity was coordinated temporally with prolonged activity in the stomach. Cisapride increased electrical and contractile activity in the left dorsal colon with increased contraction amplitude and an increase in electrical activity in the small colon. In the stomach and small intestine cisapride produced dose‐dependent increases in activity but in the left dorsal and small colon the intermediate dose (0.1 mg/kg) produced the largest and most consistent responses. Side‐effects observed were increased bowel sounds and frequency of defaecation, a slight increase in heart rate and transient signs of discomfort at the highest (0.25 mg/kg) dose rate.
Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo‐caeco‐colonic junction
Authors: RUCKEBUSCH Y. , ROGER T.
Published: April 2008

Ruckebusch, Y. & Roger, T. Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo‐caeco‐colonic junction. J. vet. Pharmacol. Therap.11, 322–329.

The electromyogram of the terminal ileum, the caecum and the proximal right ventral colon was recorded in fasted conscious ponies receiving intravenously equiactive doses of pilocarpine (0.05 mg/kg) and carbachol (0.01 mg/kg) as acetylcholine analogues; cisapride (0.1 mg/kg) and metoclopramide (2 mg/kg) facilitating acetylcholine release from myenteric neurones and naloxone (0.05 mg/kg) as an antagonist of the endogenous inhibitory opioid system. Both cisapride and naloxone induced typical migrating spike bursts in the colon associated with contractions of caecal body and caecal base. Both pilocarpine and carbachol stimulated the terminal ileum but had opposite effects on the activity of the caeco‐colonic segment which was decreased by pilocarpine and increased by carbachol. High doses of metoclopramide had weak and unspecific stimulatory motor effects. It is concluded that a true prokinetic effect at the equine ileo‐caeco‐colonic junction requires a motor profile which includes coordination between contractions sequentially involving the body and the base of the caecum and migrating spike bursts on the proximal colon. Such changes in the motor profile were produced by cisapride and naloxone and to a lesser extent by carbachol.
Comparison of serum and renal gentamicin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity
Authors: BROWN S. ANTHONY , GARRY F. B.
Published: April 2008

Anthony Brown, S., & Garry, F.B. Comparison of serum and renal gentamycin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity. J. vet. Pharmacol. Therap.11, 330–337.

Gentamicin was given to six sheep at a dosage rate of 80 mg/kg/day divided into three daily doses to cause nephrotoxicity. Peak serum gentamicin concentrations rose significantly throughout dosing (P < 0.05), but trough serum gentamicin concentrations increased dramatically (P < 0.01) from initial concentrations of 3.2–9.1 μg/ml to final trough concentrations of 31.5–195 μg/ml by 6–10 days on gentamicin. The serum gentamicin elimination half‐life (t1/2) was doubled in each animal by approximately 6 days on therapy, with the sheep that were the most clinically affected by the nephrotoxic effects of gentamicin showing increases in t1/2 earlier than those sheep that remained less intoxicated. These changes occurred before many other clinical indicators of nephrotoxicity, with only urinary enzyme excretions preceding the changes in gentamicin elimination. Thus, alterations in the elimination of gentamicin may be one of the first clinical indicators of the occurrence of gentamicin‐induced nephrotoxicity.
A comparison of the various routes of administration of erythromycin in cattle
Authors: BURROWS G. E. , GRIFFIN D. D. , PIPPIN A. , HARRIS K.
Published: April 2008

A comparison of i.v., i.m. and s.c. administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef‐type calves of approximately 200 kg body weight. Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate. Absorption of erythromycin was very slow by both the i.m. and s.c. routes of administration with a Kab of 0.0135 min‐1 and 0.0185 min‐1 for i.m. and 0.0032 min‐1 and 0.0074 min‐1 for s.c. at 15 mg/kg and 30 mg/kg, respectively. The bioavailability (32–42%) and peak serum concentrations were much lower with s.c. than with i.m. (60–65%) administration. The disposition of erythromycin administered i.v. appeared to be representative of dose‐dependent kinetics rather than dose‐independent first‐order kinetics inasmuch as the elimination half‐time (t1/2B) increased from 174.5 ± 13 min for the 15 mg/kg dosage to 239 ± 10.8 min with 30 mg/kg dosage. An acute apparent cardiovascular effect accompanied i.v. administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg. Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.
Effect of dose and route of administration of ACTH 1–24 on plasma Cortisol concentrations in ewes
Authors: ESSAWY S. A. , BENHAJ K. M. , COOKE R. G. , DOBSON H.
Published: April 2008

Doses of 0.005–1.0 mg of ACTH1–24 given intravenously, intramuscularly or as an intramuscular depot injection caused increases in Cortisol concentrations within 15 min in the plasma of ewes. There was, however, considerable animal‐to‐animal variation in maximum concentrations achieved. A curvilinear dose‐response relationship to ACTH1–24 was obtained which was similar for each route of administration when expressed in terms of maximum Cortisol concentrations. However, for a given dose, more prolonged release of Cortisol occurred after i.m. injection compared to i.v., with maximum concentrations occurring 6 h after the depot formulation injection. Five repeated daily doses of 1.0 mg depot ACTH1–24 resulted in no diminution of Cortisol response indicating considerable synthesizing capacity of the adrenals in clinically normal ewes. Comparison of cortisol concentrations after an acute stressor (shearing) suggests that doses of ACTH1–24 greater than 0.25 mg are excessive for simulation of stress‐induced adrenal activity.
Pharmacokinetic disposition of an immediate‐release aminophylline and a sustained‐release theophylline formulation in the horse
Authors: GOETZ T. E. , MUNSIFF I.J. , McKIERNAN B. C.
Published: April 2008

The pharmacokinetic disposition of theophylline was determined by high‐performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate‐release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained‐release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (Λz), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 ± 0.01 h‐1, 0.80 ± 0.06 l/kg, and 0.06 ± 0.01 l/kg/h (mean ± SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P < 0.05) for the immediate‐release aminophylline (13.8 ± 2.8 h) and sustained‐release theophylline (18.2 ± 2.3 h) formulation. Immediate‐release aminophylline tablets quickly achieved peak theophylline plasma concentrations of 11.51 ± 1.4 μg/ml at 1–6 ± 0.6 h while the sustained‐release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 ± 1.3 μg/ml at 7.3 ± 1.0 h. Absolute bioavailability was 87% for the immediate‐release and 97% for the sustained‐release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained‐release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough–peak theophylline plasma concentrations between 6 and 17 μg/ml.
The disposition of albendazole in sheep
Authors: HENNESSY D. R. , STEEL J. W. , LACEY E. , EAGLESON G. K. , PRICHARD R. K.
Published: April 2008

Albendazole (ABZ) was administered intraruminally at 4.75 mg/kg to sheep fitted with a permanent bile‐duct cannula to determine if its metabolites might contribute to its flukicidal action. ABZ metabolism was consistent with first‐pass clearance by the liver, resulting in ABZ sulphoxide (ABZ‐SO) and ABZ sulphone (ABZ‐SO2) being present in plasma at maximum concentrations (meanCmax± SD) of 2.0 ± 0.2 μg/ml and 0.4 ± 0.1 μg/ml after 8 ± 3 h and 24 ± 5 h, respectively. ABZ‐SO, but more particularly ABZ‐SO2, appeared to bind to plasma proteins but their clearance rates from plasma were similar. Biliary ABZ metabolites were mainly unconjugated ABZ‐SO and 2OH‐ABZ‐SO (8.0% dose) or conjugated glucuronide and sulphate esters (6.3% dose) mainly of 2OH‐ABZ‐SO and 2OH‐ABZ‐SO2. The concentration of the major biliary metabolite, unconjugated ABZ‐SO, followed a similar time profile to that of ABZ‐SO in plasma except thatCmaxwas much higher (6.2 ± 2.2 μg/ml). Intraruminal administration of ABZ reduced bile flow rate by 30% which may be attributable to an inhibitory effect of ABZ on microtubule formation in hepatic secretory cells. It is suggested that ABZ is sequestered in the liver. This is unlikely to contribute to its flukicidal action, which is probably attributable to ingestion of ABZ‐SO from bile and blood by the fluke.
Central and peripheral β‐adrenergic influences on reticulo‐rumen and upper‐gut myoelectrical activity in sheep
Authors: BRIKAS P. , BUÉNO L. , FIORAMONTI J.
Published: April 2008

The effects of intravenous (i.v.) and intracerebroventricular (i.e.v.) administration of β‐adrenoceptor agonists were evaluated on the reticulo‐rumen and upper‐gut myoelectrical activity in six ewes chronically fitted with intraparietal electrodes and a cannula in a lateral ventricle of the brain. Intravenous infusion of the β1 agonist dobutamine (30 μg/kg/min for 15 min) reduced the frequency of reticulo‐ruminal and abomasal contractions and stimulated duodeno‐jejunal motility, inducing a Phase III on the jejunum. These effects were reproduced by i.c.v. dobutamine at a dose of 10 μg/kg. Intravenous infusion of the β2 agonist ritodrine (15 μg/kg/min for 15 min) selectively inhibited antral and duodenal motility. Ritodrine i.c.v. (15 μg/kg) did not affect forestomach or gastrointestinal motility. The mixed β1, β2 agonist isoprenaline infused i.v. (0.6 μg/kg/min for 15 min) reproduced the effects of i.v. dobutamine, except at the antro‐duodenal level which was strongly inhibited. The effects of i.v. dobutamine were antagonized by i.v. or i.c.v. acebutolol, a specific β1 antagonist. The effects of i.v. ritodrine were blocked by i.v. but not i.c.v. administration of propranolol, a mixed β1, β2 antagonist. These data indicate that the stimulation of central β1 adrenoceptors inhibits forestomach and antral motility and stimulates duodeno‐jejunal motility. Stimulation of peripheral β2 adrenoceptors selectively inhibits duodeno‐jejunal motility.
Pharmacokinetics of tinidazole in the horse
Authors: PYÖRÄLÄ S. , KOTILAINEN T. , SILVENNOINEN P. , HÄNNINEN U. , MERO M. , KAARTINEN L.
Published: April 2008

Serum tinidazole concentrations were monitored in five clinically healthy adult horses after intravenous (i.v.) and oral administration of the drug (15 mg/kg and 25 mg/kg, respectively). After i.v. administration, the mean residence time was 7.0 h, the elimination half‐life 5.2 h and the body clearance rate 1.6 ml/min/kg. The distribution volume was found to be 660 ml/kg. After oral administration, the mean residence time was 8.5 h, the absorption half‐life 1.1 h and the bioavailability essentially 100%. In view of the in‐vitro sensitivities of various anaerobic bacteria, a dosage of 10‐15 mg/kg of tinidazole, orally, at 12‐h intervals, can be recommended for the treatment of anaerobic infections in horses.
Central and peripheral α‐adrenoceptor actions of amitraz in the dog
Authors: CULLEN L. K. , REYNOLDSON J. A.
Published: April 2008

The aim of this study was to determine the contribution of α2‐and α1 adrenoceptor agonist activity of the formamidine, amitraz, on peripheral circulation in the dog. Intra‐arterial injections of amitraz (0.25‐5.0 μg/kg) produced a dose‐dependent increase in perfusion pressure in the autoperfused hind limbs of methoxyflurane‐anaesthetized dogs. A constant blood flow to the hind limbs was maintained using a peristaltic pump. Intravenous phentolamine (0.5 mg/kg), prazosin (35 μg/kg) and yohimbine (10 μg/kg) in separate experiments antagonized the vasoconstrictor actions of amitraz and produced a parallel shift to the right of the amitraz dose‐response curve. Cumulative doses of amitraz (0.5‐15 μg/kg) given by intracisterna magna (i.c.m.) injections reduced mean arterial pressure and heart rate in a dose‐dependent manner. Similar responses were produced by intravenous amitraz but at much higher doses. In separate experiments amitraz‐induced hypotension (doses up to 25 μg/kg i.c.m.) was prevented by pre‐treatment with yohimbine (30 μg/kg i.c.m.) but not prazosin (20 μg/kg i.c.m.). Both antagonists partially inhibited the bradycardia produced by amitraz. It is concluded that amitraz stimulates α1‐and α2‐adrenoceptors to produce vascular constriction. The central hypotensive action of amitraz appears to be mediated by α2‐adrenoceptors; however, both receptor subtypes appear to be stimulated to produce bradycardia.
Apomorphine‐induced emesis in the dog‐routes of administration, efficacy and synergism by naloxone
Authors: SCHERKL R. , HASHEM A. , FREY H.‐H.
Published: April 2008

Scherkl, R., Hashem, A. & Frey, H.‐H. Apomorphine‐induced emesis in the dog‐routes of administration, efficacy and synergism by naloxone. J. vet. Pharmacol. Therap. 13, 154–158.

Apomorphine proved to be more effective as an emetic in dogs after s.c. administration than after i.m. injection with doses of 0.04 and 0.1 mg/kg. This effect is explained by an anti‐emetic effect mediated by μ‐receptors in the vomiting centre in die brain, which, in contrast to the chemoreceptor trigger zone, is within the blood‐brain barrier. A certain delay between the stimulation of D2‐receptors in the chemoreceptor trigger zone (causing emesis) and μ‐receptors in the vomiting centre (producing anti‐emesis) therefore results, leading to a self‐limiting emesis. Blockade of the μ‐receptors by naloxone increased and prolonged the effect of apomorphine. A relatively narrow range of apomorphine concentrations on s.c. administration is then effective to stimulate the chemoreceptor trigger zone, but can hardly inhibit the vomiting centre, and must therefore be considered the most suitable route for administration of apomorphine.

R. Scherkl, Department of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstr. 20, D‐1000, West Berlin, FRG.
Pharmacokinetics of fenbendazole in dogs
Authors: McKELLAR Q. A. , HARRISON P. , GALBRAITH E. A. , INGLIS H.
Published: April 2008

McKellar, Q.A., Harrison, P., Galbraith, E.A. & Inglis, H. Pharmacokinetics of fenbendazole in dogs. J. vet. Pharmacol. Therap. 13, 386–392.

Fenbendazole was administered to dogs at a dose rate of 20 mg/kg body weight on a single occasion in gelatin capsules, on 5 consecutive days in feed, and on a single occasion as an alginate suspension. It was also administered at a dose rate of 100 mg/kg body weight on a single occasion in feed. Following single administration of 20 mg/kg fenbendazole mean maximum concentrations (Cmax) of the parent drug and its known active sulphoxide metabolite were 0.42 ± 0.05 and 0.31 ± 0.05 μg/ml, respectively. Mean times until maximum concentrations were achieved (tmax) were 12.67 ± 4.18 and 15.33 ± 2.81 h, respectively, and areas under the plasma concentration‐time curves (AUC) were 5.83 ± 0.65 and 4.60 ± 0.57μg.h/ml, respectively. Administration in feed increased the apparent bioavailability and administration for 5 consecutive days provided sustained plasma concentrations, generally > 0.2μg/ml. Administration as an alginate did not increase bioavailability or extend the persistence in plasma. It did increase the tmax to 16.80 ± 2.93 and 20.00 ± 2.53 h for fenbendazole and its sulphoxide metabolite, respectively. Increasing the dose from 20mg/kg to 100mg/kg did not substantially increase the Cmax or AUC.

Q. A. McKellar, Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow G61 1QH, UK.
Comparative pharmacokinetics of doxycycline in cats and dogs
Authors: RIOND J.‐L. , VADEN S. L. , RIVIERE J. E.
Published: April 2008

Riond, J.‐L., Vaden, S.L. & Riviere, J.E. Comparative pharmacokinetics of doxycycline in cats and dogs.J. vet. Pharmacol. Therap.13, 415–424.

The disposition of doxycycline hyclate was studied in six adult mixed‐breed female cats and six adult mid‐sized female dogs following a single intravenous administration of 5 mg/kg body weight. Doxycycline volume of the central compartment, area volume of distribution, volume of distribution at steady state, and total body clearance were significantly smaller in cats. The differences were attributed to more extensive binding of doxycycline to plasma protein including albumin in cats. The significant differences in the volume of distribution and total body clearance were not reflected in elimination half‐lives under the conditions of this study (sample size, inhomogeneous population). Doxycycline elimination half‐life was 4.56±0.68 (SEM)h for cats and 6.99±1.09h for dogs. Dosage regimens recommended in the veterinary literature were evaluated by the computer program PETDR.

Dr J. E. Riviere, Laboratory of Toxicokinetics, Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina Stale University, Raleigh, NC 27606, USA.
Comparative in vitro susceptibility of Bacteroides and Fusobacterium isolated from footrot in sheep to 28 antimicrobial agents
Authors: DURÁN S. PÍRIZ , VALERA R. CUENCA , MANZANO J. VALLE , MACHOTA S. VADILLO
Published: April 2008

The agar dilution method was used to determine the bacteriostatic activity of 28 antimicrobial agents against 141 strains to the genus Bacteroides and 29 strains from the genus Fusobacterium. All organisms were isolated from clinical cases of ovine footrot. The strains were isolated from 125 Merino sheep, over a period of 2 years, from January 1987 to December 1988. The three ureidopenicillins studied (azlocillin, mezlocillin and piperacillin) proved to be the most effective antimicrobial agents. Chloramphenicol, metronidazole and tinidazole effectively inhibited the growth of Bacteroides spp., while phosphomycin was active against Fusobacterium spp.
Clenbuterol plasma concentrations after repeated oral administration and its effects on cardio‐respiratory and blood lactate responses to exercise in healthy Standardbred horses
Authors: KALLINGS P. , INGVAST‐LARSSO C. , PERSSON S. , APPELGREN L‐E. , FÖRSTER H. J. , ROMINGER K. L.
Published: April 2008

To evaluate the effects of clenbuterol on cardio‐respiratory parameters and blood lactate relation to exercise tolerance, experimental horses performed standardized exercise tests on a high‐speed treadmill before and after administration of the drug. Clenbuterol was administered in feed to six healthy Siandardbrecls at a dose rale of 0.8 μg/kg b.wt twice daily for 5.5 days. Each horse was tested twice, without and with a respiratory mask, during two consecutive days. One week elapsed between the baseline tests without drug and the tests with clenbuterol treatment (each horse served as its own control). The results show an unchanged heart rate response to exercise 2 h after the last clenbuterol administration. The blood lactate response and the arterial oxygen tension during exercise did not differ before and after drug treatment. The oxygen uptake as well as pulmonary ventilation relative to the work load performed was essentially unaffected. The arterial pH during exercise was significantly increased (P < 0.05) following clenbuterol treatment. Plasma levels of clenbuterol were maximal 2 h post‐administration with values between 0.45 and 0.75 ng/ml. The plasma half‐life of elimination was 10.4 h (± 2.25 SD). In conclusion, clenbuterol did not cause any major effects on the cardio‐respiratory and blood lactate parameters studied in healthy horses performing submaximal exercise tolerance tests.
Alpha‐2 adrenoreceptors mediate clonidine‐induced hypoinsulinaemia in sheep
Authors: OSMAN T. E. A. , NICHOLSON T.
Published: April 2008

Insulin and glucose concentrations in the blood of sheep were measured before, and up to 7 h after, feeding. The patterns reported by other workers were confirmed, namely: an early insulin concentration peak and decline in glucose concentration and, later, more prolonged changes. Intravenous injection of clonidine (2 μg/kg or 5 μg/kg) just before offering food caused hypoinsulinaemia and hyperglycaemia, abolishing the normal patterns. Administration of idazoxan (0.1 mg kg‐1), an alpha‐2 adrenoreceptor antagonist, before a 2 μg/kg dose of clonidine, completely blocked the effects of clonidine. By contrast, with prior injection of prazosin (0.1 mg/kg), an alpha‐1 adrenoreceptor antagonist, the hypoinsulinaemia in response to clonidine still occurred and the hyperglycaemia appeared to be enhanced. The antagonists injected alone had only slight effects: idazoxan caused a slight hypoglycaemia and prazosin a slight hyperglycaemia. The results indicate that clonidine causes hypoinsulinaemia and hyperglycaemia by action on alpha‐2 receptors. Possible mechanisms are discussed.