bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of jingsongling, a xylazine analog, on mean arterial blood pressure and heart rate in dogs — influences of yohimbine, tolazoline, prazosin, and atropine
Authors: HSU W. H. , RONG YAO‐FANG , HEMBROUGH F. B.
Published: April 2008

The effects of jingsongling (JSL) and xylazine on heart rate (HR) and mean arterial pressure (MAP) were studied in five conscious male dogs. An i.v. injection of xylazine (1 mg/kg) caused a bradycardia, an initial hypertension, and a subsequent hypotension. An i.v. injection of JSL (1 mg/kg) caused a bradycardia and a 20‐min hypertension without a subsequent hypotension. Atropine sulfate (45 μg/kg, i.v.) increased HR for 30 min without changing MAP, and antagonized JSL‐induced bradycardia for at least 60 min. There was a subsequent rebound bradycardia. Atropine sulfate potentiated JSL‐induced hypertension in both magnitude and duration. Yohimbine (0.1 mg/kg, i.v.), an α2‐adrenoceptor antagonist, increased HR and MAP for 110 and 70 min, respectively. Yohimbine not only failed to potentiate but even reversed the pressor effect of JSL in a dose‐dependent manner. Yohimbine also caused a dose‐dependent reversal of JSL‐induced bradycardia. Tolazoline (5 mg/kg, i.v.), a nonselective α‐adrenoceptor antagonist, increased MAP for 20 min without changing HR. Tolazoline also reversed JSL‐induced hypertension and bradycardia. Prazosin (1 mg/kg), an α1‐adrenoceptor antagonist, decreased MAP and increased HR for at least 110 min. Prazosin reversed JSL‐induced hypertension but failed to affect JSL‐induced bradycardia. These results indicated that: (1) JSL‐induced bradycardia and hypertension are mediated by α2‐adrenoceptors; (2) yohimbine and tolazoline may be useful in antagonizing these untoward reactions associated with JSL administration, whereas prazosin and atropine were not found to be beneficial in this regard.
Effect of flunixin meglumine on prostaglandin F2α synthesis and metabolism in the pig
Authors: ODENSVIK K. , CORT N. , BASU S. , KINDAHL H.
Published: April 2008

The effect of flunixin meglumine on prostaglandin synthesis and metabolism was evaluated in the pig in vivo. It was found that the prostaglandin metabolite, 15‐ketodihydro‐PGF2α, was decreased in the peripheral circulation within 20 min of injection of the drug. In therapeutic doses in the pig the drug had no effect on the metabolism of PGF2α. Flunixin was compared with some other non‐steroidal anti‐inflammatory drugs in an in vitro test system utilizing sheep vesicular gland microsomes. It was concluded that this drug is a potent inhibitor of prostaglandin synthesis.
Opioid modulation of tonic luteinizing hormone release in ovariectomized dairy cows
Authors: NANDA A. S. , WARD W. R. , DOBSON H.
Published: April 2008

A possible role of endogenous opioid peptides (EOP) in regulating the release of luteinizing hormone (LH) in the absence of ovarian influence was investigated. Experiments were conducted on three lactating Holstein–Friesian dairy cows, 20–27 days after ovariectomy. The cows were bled before and after a single intravenous (i.v.) injection of either 250 mg of naloxone (EOP antagonist) or 300 mg of morphine (EOP agonist) or a combination of the two in Experiments 1, 2 and 3, respectively. The mean and basal LH concentrations and the LH pulse frequency and amplitude were compared before and after each treatment in each cow. Naloxone induced an immediate rise in LH concentration by 60–300% above the preceding baseline values. This rise lasted for 15–30 min in each cow, after which the normal rhythmic LH release continued. One cow (A) suffered discomfort and respiratory distress 15–25 min after naloxone administration and the mean and basal LH concentration dropped significantly. Morphine significantly reduced the mean LH concentration by decreasing the number and amplitude of LH pulses and the basal LH values in two cows, although the decrease in one was not significant. The mean LH concentration in each cow remained unaffected by the combined treatment of morphine and naloxone. In conclusion, the elevation of LH concentration by naloxone, the suppression of LH release by morphine and the reversal by morphine and naloxone of each other's effects suggest that EOP could be involved in the control of LH release in cows in the absence of ovarian influence.
Effect of calcium‐channel blockers and salbutamol on the isolated mare uterus — interaction with the calcium agonist Bay K 8644
Authors: CORUZZI G. , POLI E. , BERTACCINI G.
Published: April 2008

The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium‐channel blockers and salbutamol inhibited the spontaneous, KC1‐ and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10‐8‐10‐6 mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2 value = 8.54 ± 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium‐channel blockers are potent inhibitors of mare uterine motility in vitro and emphasize the importance of Ca2+‐related mechanisms in the control of uterine smooth‐muscle contractility. Moreover, the validity of Bay K 8644 as a tool to distinguish classes of calcium‐channel antagonists is confirmed.
Absorption of two trimethoprim/sulphonamide combinations from the uterus of pony mares
Authors: BOYD E. H. , ALLEN W. E.
Published: April 2008

Plasma drug concentrations were measured after two commercially available potentiated sulphonamides, trimethoprim and sulfadoxine and trimethoprim and sulphadiazine, were infused daily for 2 and 3 days, respectively, into the uteri of pony mares which had been mated before ovulation. Intravenous administration of trimethoprim and sulfadoxine allowed uterine absorption of trimethoprim (23–43%) and sulfadoxine (29–34%) to be calculated. After intrauterine administration trimethoprim and sulphadiazine were detected in the milk of a lactating mare. In order to maintain plasma concentrations likely to be required for clinical efficacy of both drugs they should be administered every 12 h. However, infusions of both preparations caused endometrial inflammation as assessed by cytological and histological examination and this may have been responsible for the low pregnancy rate.
Construction of best confidence intervals for half‐lives
Authors: BARTOSZYŃSKI R. , POWERS J. D.
Published: April 2008

This paper presents a method of determining a confidence interval for the drug half‐life based on statistical properties of the estimates of the disappearance rate constant of the drug. This interval is shown to be of minimum length which indicates it is a more precise estimate than others currently in use. A computer program to construct these intervals is available upon request.
Reversal of medetomidine sedation by atipamezole in dogs
Authors: VAINIO O. , VÄHÄ‐VAHE T.
Published: April 2008

Atipamezole reversed the sedative effect of medetomidine in twelve laboratory beagles. The dogs were sedated with medetomidine doses of 20, 40 and 80 μg/kg body wt i.m. Atipamezole was injected (i.m.) 20 min later at dose rates two, four, six and ten times higher (in μg/kg) than the preceding medetomidine dose. Placebo treatment was included in the study. The deeply sedated dogs showed signs of arousal in 3‐7 min and took their first steps 4‐12 min after atipamezole injection. The dose‐related reversal effect of atipamezole proved to be optimal with doses which were four, six or ten times higher than the preceding medetomidine dose. Drowsiness was found 0.5‐1 h after atipamezole injection in 41% of the cases. No adverse effects nor cases of over‐alertness or excitement were found.
The cardiorespiratory effects of intrathecal xylazine in the conscious rabbit
Authors: NOLAN A. M. , ERHARDT W.
Published: April 2008

The α2 agonist xylazine produced a dose‐dependent decrease in mean arterial blood pressure in conscious rabbits when injected intrathecally (i.t.) through a cannula previously implanted under general anaesthesia. Intrathecal administration of 200 and 400 μg of xylazine produced a significant reduction in arterial blood pressure from control values (maximum depressions of 25% and 33%, respectively). There was little effect on cardiac output and arterial carbon‐dioxide tension and no effect on respiratory rate, arterial oxygen tension and pulse rate. Intrathecal injection of 100 μl of 0.9% saline had no effect. Intravenous (i.v.) tolazoline (0.5 mg/kg) abolished xylazine‐induced hypotension (200 μg) in four rabbits. Contrast radiography revealed that 100 μl of solution injected i.t. in anaesthetized rabbits spread distally over eight vertebral spaces. There was little rostral spread. It was concluded that xylazine‐induced hypotension following i.t. injection was due to local activation of α2 adrenoceptors present in the thoracic spinal cord. It is postulated that spinal α2 adrenoceptors may play an important role in the hypotension recorded in animals after parenteral injection of xylazine.
Effects of experimentally induced Streptococcus suis infection on the pharmacokinetics of penicillin G in pigs
Authors: ZHEN‐LING ZENG , KI‐FAI FUNG
Published: April 2008

The pharmacokinetics of potassium penicillin G were studied in both healthy (n = 8) and experimentally Streptococcus‐suis‐infeaed (n = 6) pigs following intramuscular administration (15 000 iu/kg). Streptococcus‐suis infection was induced artificially in young cross‐bred pigs by subcutaneous inoculation with 9 × 108 to 109 colony‐forming units of S. suis. The rectal temperature of infected pigs was significantly increased (P < 0.01) before penicillin G injection and this was maintained for 8 h after the drug was given. Other clinical symptoms were also present. The serum concentration‐time data for penicillin were found to fit a one‐compartment open model with first‐order absorption in the two groups of pigs. Significant changes were not observed between healthy and diseased pigs in following parameters: A, Ka, Ke and Tmax‐However, in diseased pigs, significant increases (P < 0.01) were found in Vd and ClB, and significant decreases (P < 0.01) in Cmax and AUC occurred. The increased body clearance (ClB) and greater apparent volume of distribution (Vd) of penicillin G could partly explain why the serum values of the drug were much lower in diseased pigs than in healthy pigs.
Copper salicylate and copper phenylbutazone as topically applied anti‐inflammatory agents in the rat and horse
Authors: AUER D. E. , NG J. C. , SEAWRIGHT A. A.
Published: April 2008

Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as antiinflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti‐inflammatory effect of the drugs were assessed by measuring changes in the paw or alar‐fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior antiinflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 μg/ml) and negligible concentrations of oxyphenbutazone and ß‐hydroxyphenylbuta‐zone were detected in the plasma.
The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses
Authors: STEVENSON A.J. , WEBER M. P. , TODI F. , MENDONCA M. , FENWICK J. D. , KWONG R. E. , YOUNG L. , LEAVITT R. , NESPOLO T R. , BEAUMIER T P. , TIMMINGS S. , KACEW S.
Published: April 2008

A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre‐treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2‐6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fentanyl, the data generated were insufficient to state with certainty whether or not furosemide affected the plasma concentrations of these three drugs. A significant reduction was noted in the urinary concentrations of guaifenesin, acepromazine, clenbuterol, phenylbutazone, flunixin, fentanyl and pentazocine within 1‐4 h of furosemide administration. The urinary concentrations of theophylline remained reduced as long as 8 h after furosemide injection. Furosemide administration to horses pre‐treated with codeine resulted in depression of urinary morphine concentrations 2‐4 h and 9‐12 h after furosemide injection. A lower furosemide dose (150 mg) produced changes in drug urinary excretion and plasma elimination equivalent to the higher dose (250 mg). It is evident that furosemide affects the urinary and plasma concentrations of other co‐administered drugs but not in a predictable fashion, which limits the extrapolation of these results to as yet untested drugs.
The effect of clinical hepatic disease on the distribution and elimination of pethidine administered post‐operatively to dogs
Authors: WATERMAN A. E. , KALTHUM W.
Published: April 2008

Waterman, A.E. & Kalthum, W. The effect of clinical hepatic disease on the distribution and elimination of pethidine administered post‐operatively to dogs. J. vet. Pharmacol. Therap. 13, 137–147.

The pharmacokinetics of pethidine were investigated in dogs suffering from portosystemic vascular shunts and hepatic parenchymal disease. The drug was administered post‐operatively at a dose rate of 2.0 mg/kg either intravenously or intramuscularly. When the drug was given intravenously to dogs suffering from intrahepatic shunts, the elimination half life was 75.5 ± 4.2 min and the clearance rate was 29.0 ± 2.3 ml/kg min. When the drug was given intramuscularly its rate of absorption was very slow (57.9 ± 6.1 min) and the time taken to reach the maximum plasma concentration was long at 26.7 ± 6.4 min. The elimination half‐life for the intramuscularly administered drug was also very slow at 108.0 ± 13 min, reflecting the reduced ability of these dogs to metabolize and eliminate pethidine. These findings suggest that caution should be exercised in the administration of pethidine to dogs suffering from hepatic dysfunction. In particular, the slower rate of absorption should be remembered in judging whether or not maximum effects have been achieved and the longer elimination half‐life indicates the need to extend the intervals between repeat doses of this analgesic.

A. E. Waterman, Department of Veterinary Surgery, University of Bristol, Langford House, Langford, Bristol BS18 7DU, UK.
Gastric retention of enteric‐coated aspirin tablets in beagle dogs
Authors: NAP R. C. , BREEN D.J. , LAM T. J. G. M. , De BRUYNE J.J.
Published: April 2008

Nap, R.C., Breen, D.J., Lam, T.J.G.M. & de Bruyne, J.J. Gastric retention of enteric‐coated aspirin tablets in beagle dogs. J. vet. Pharmacol. Therap. 13, 148–153.

Administration of acetylsalicyclic acid (ASA) in the dog may cause gastric mucosal damage. Enteric‐coated tablets protect the canine stomach during oral ASA medication. A therapeutic plasma salicylate concentration can be attained using enteric‐coated ASA tablets at a dose rate of 25 mg/kg body wt, administered every 8 h. Six beagle dogs were given enteric‐coated ASA tablets (500 mg) orally, in a 5‐day cross‐over experiment on two different feeding regimens: i.e. feeding once daily (Group I) or 8 hourly (Group II). Results demonstrate that feeding regimen strongly influences the plasma salicylate concentration pattern. Subtherapeutic mean plasma salicylate concentrations were found in both groups. In Group II the standard deviation (SD) of the mean plasma salicylate concentration was larger than that of Group I. The minimal plasma salicylate concentration never reached detectable levels in Group II. In both groups large numbers of tablets were vomited. Gastric evacuation of the ASA tablets is comparable to indigestible solid particles; their removal was dependent on the interdigestive gastric motility. It is concluded that large enteric‐coated ASA tablets are not suitable for therapeutic use in small dogs.

R. C. Nap, Department of Clinical Sciences of Companion Animals, Uirechl University, PO Box 80. 154, 3508 TD, Utrecht, the Netherlands
The effect of phenylbutazone on the plasma disposition of penicillin G in the horse
Authors: FIRTH E. C. , NOUWS J. F. M. , KLEIN W. R. , DRIESSENS F.
Published: April 2008

Firth, E.C., Nouws, J.F.M., Klein, W.R. & Driessens, F. The effect of phenylbutazone on the plasma disposition of penicillin G in the horse. J. vet. Pharmacol. Therap. 13, 179–185.

A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.

E. C. Firth, Veterinary Surgery and Companion Animal Health, Department of Clinical Sciences, Faculty of Veterinary Science, Massey University, Palmerston North, New Zealand.
Effects of non‐steroidal anti‐inflammatory drugs on canine neutrophil chemotaxis
Authors: STRØM H. , THOMSEN M. KROGSGAARD
Published: April 2008

Strøm, H. & Krogsgaard Thomsen, M. Effects of non‐steroidal anti‐inflammatory drugs on canine neutrophil chemotaxis. J. vet. Pharmacol. Therap. 13, 186–191.

Non‐steroidal anti‐inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in‐vitro and ex‐vivo effects of phenylbutazone and flunixin on leukotriene‐B4‐directed migration of canine PMN. Furthermore, in‐vitro comparison was made to indomethacin and the 5‐lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro, flunixin and NDGA were the most potent inhibitors, with IC50s of 13 and 7 μmol/l, respectively. Phenylbutazone had an IC50 of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l. Ex vivo, flunixin almost completely abolished the LTB4 response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti‐inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.

M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products, DK‐2750, Ballerup, Denmark.
Pharmacokinetics of sulfadimidine and its N4‐acetyl metabolite in healthy and diseased rabbits infected with Pasteurella multocida
Authors: YUAN ZHONG‐HUI , FUNG KI‐FAI
Published: April 2008

Yuan, Zhong‐Hui & Fung, Ki‐Fai. Pharmacokinetics of sulfadimidine and its N4‐acetyl metabolite in healthy and diseased rabbits infected with Pasteurella multocida. J. vet. Pharmacol. Therap. 13, 192–197.

The pharmacokinetics of sulfadimidine (SDM) and its N4‐acetyl metabolite (N4SDM) were investigated after intravenous bolus injection of a single dose (200mg/kg) of SDM in normal and diseased New Zealand white rabbits. The apparent distribution volume at steady state, total body clearance and elimination half‐life of SDM in normal animals were 0.7±0.3l/kg, 0.57±0.24 l/kg/h and 1.6±1.3h, respectively. Of the administered dose, 62.1% was metabolized by N4‐acetylation, and 12.7±1.1 and 2.8±1.8% of the dose was excreted as free drug by the kidney and gastrointestinal tract, respectively. The ‘apparent’ formation and elimination half‐lives of N4‐SDM were 0.6±0.4 and 2.2±1.1h, respectively. The metabolite was eliminated mainly by excretion through the kidney. There was no significant effect of acute pasteurellosis on the pharmacokinetics of either SDM or N4SDM in rabbits.

Yuan Zhong‐Hui, Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Effects of nitrofurans on adrenal cortical tissue in chickens
Authors: BARTLET A. L. , KHAN F. H.
Published: April 2008

Bartlet, A.L. & Khan, F.H. Effects of nitrofurans on adrenal cortical tissue in chickens. J. vet. Pharmacol. Therap. 13, 206–216.

In chicken adrenal glands, aspartate transaminase (AST) activity is concentrated in the adrenal cortical cells. Administration of a bolus dose of furazolidone (200mg/kg) to the birds produced a decrease in AST activity in the adrenal glands and a general disorganization in the ultrastructure of the adrenal cortical cells. Many adrenal cortical mitochondria appeared to be moribund, being swollen, without cristae or apparently empty. These effects preceded atrophy of the adrenal cortical tissue, which was most marked in the central part of the adrenal glands. The atrophy was still present after 12 weeks, and it is therefore suggested that nitrofurans may be useful in the treatment of Cushing's disease in other animal species. When furazolidone or furaltadone was given in the diet at therapeutic levels, blebs of an electron‐dense substance developed in adrenal cortical mitochondria and AST activity in the adrenal glands was reduced. These effects were found to be reversible, and the treatments did not produce atrophy of the adrenal cortical tissue.

A. L. Bartlet, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Edinburgh, Edinburgh EH9 IQH, UK.
Contrasting effects of nitrofurans on plasma corticosterone in chickens following administration as a bolus or diet additive
Authors: BARTLET A. L. , HARVEY S. , KLANDORF H.
Published: April 2008

Bartlet, A.L., Harvey, S. & Klandorf, H. Contrasting effects of nitrofurans on plasma corticosterone in chickens following administration as a bolus or diet additive. J. vet. Pharmacol. Tlierap. 13, 261–269.

Administration of furazolidone as a bolus dose (8–500 mg/kg), produced a decrease in plasma corticosterone in chickens. In contrast, addition of furazolidone or furaltadone to the diet (0.04% or above, 10 days), increased plasma corticosterone. Pre‐treatment with a 200‐mg/kg bolus of furazolidone or furaltadone did not affect pentobarbitone anaesthesia time in the birds. In chickens pre‐treated with a nitrofuran in the diet, however, pentobarbitone anaesthesia time was significantly less than that in controls. Furaltadone in the diet, produced significant increases in the amount of cytochrome P‐450 and the activity of aniline hydroxylase in the liver microsomes. It is suggested that nitrofurans given in the diet stimulated corticosterone biosynthesis in the adrenal glands and induced mixed‐function oxidase activity in the liver. Nitrofurans given as a bolus did not produce these effects. Furazolidone (200 mg/kg) produced severe anorexia, which lasted 2 days in T‐line birds. The anorexia seemed to be associated with tissue damage in the birds rather than the ensuing adrenal cortical insufficiency.

A. L. Bartlet, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Edinburgh, Edinburgh EH9 1QH, UK.
Tissue concentrations of clindamycin after multiple oral doses in normal cats
Authors: BROWN S. A. , ZAYA M.J. , DIERINGER T. M. , HUNTER R. P. , NAPPIER J. L. , HOFFMAN G. A. , HORNISH R. E. , YEIN F. S.
Published: April 2008

Brown, S.A., Zaya, M.J., Dieringer, T.M., Hunter, R.P., Nappier, J.L., Hoffman, G.A., Hornish, R.E. & Yein, F.S. Tissue concentrations of clindamycin after multiple oral doses in normal cats. J. vet. Pharmacol. Therap. 13, 270–277.

Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid‐phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug‐naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N‐desmethylclindamycin, its active metabolite, was done using gas‐chromatography‐mass‐spectrometry. Concentrations were highest in the lung, with tissue: serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P< 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissuerserum ratio was < 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle.

Dr Scott Anthony Brown, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A<M University, College Station, TX 77843, USA.
Chronopharmacokinetics of theophylline in the cat
Authors: DYE J. A. , McKIERNAN B. C. , NEFF‐DAVIS C. A. , KORITZ G. D.
Published: April 2008

Dye, J.A., McKiernan, B.C., Neff‐Davis, C.A. & Koritz, G.D. Chronopharmacokinetics of theophylline in the cat. J. vet. Pharmacol. Therap. 13, 278–286.

Studies of theophylline pharmacokinetics in humans have shown that a higher peak concentration and area under the curve (AUC), with a shorter time to peak (tp) occur after a morning dose than after an evening dose. The purpose of this study was to determine whether theophylline pharmacokinetics in the cat were also influenced by the administration time of day. Theophylline was administered to six cats in a three‐way cross‐over study as a single dose of intravenous aminophylline and oral sustained‐release theophylline (Slo‐bid Gyrocapsr̀ and Theo‐Durr̀ Tablets), between 08.00–09.00 h (Phase I) and 20.00–21.00 h (Phase II). Subjects were maintained on a 12‐h light (08.00–20.00 h):12‐h dark cycle. Similar to the human studies, the tp was shorter following the morning dose. Conversely, however, the peak plasma theophylline concentrations achieved in these cats following intravenous aminophylline and oral Slo‐bidr̀ were significantly higher following the evening dose. The AUC obtained for Theo‐Durr̀ was also significantly greater following the evening dose. No single pharmacokinetic parameter could account for the higher plasma concentrations achieved following the evening dose.

J. A. Dye, Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61801, USA.
Antagonism of endotoxin‐induced disruption of equine gastrointestinal motility with the platelet‐activating factor antagonist WEB 2086
Authors: KING J. N. , GERRING E. L.
Published: April 2008

King, J.N. & Gerring, E.L. Antagonism of endotoxin‐induced disruption of equine gastrointestinal motility with the platelet‐activating factor antagonist WEB 2086. J. vet. Pharmacol. Therap. 13, 333–339.

The effect of pre‐treatment with a selective platelet‐activating factor (PAF) antagonist, WEB 2086, on the actions of low‐dose endotoxin was evaluated in ponies prepared with gastrointestinal strain gauges. Endotoxin (0.1 μg/kg i.v.) produced a marked reduction in gastric contraction amplitude and rate, and an increased frequency and reduced duration of jejunal phase III activity fronts (AFs). WEB 2086 (6.6 mg/kg) administered i.v. 10 min before the endotoxin, produced significant antagonism (P < 0.001) of the effect of endotoxin on gastric contraction amplitude and rate. The combination of WEB 2086 and endotoxin produced gastric contractions of significantly (P < 0.01) higher frequency than in the control studies. WEB 2086 also reduced endotoxin‐induced abnormal phase III AFs in the jejunum and increases in heart rate and packed cell volume. These results provide evidence that endogenous PAF plays a role in mediating the acute effects of endotoxin on equine gastrointestinal motility.

J. N. King, Centre de Recherches Agricoles, CH‐1566 St‐Aubin FR, Switzerland.
Pharmacokinetics of intravenously, intramuscularly and intra‐adiposely administered carazolol in pigs
Authors: KADIR F. , ZUIDEMA J. , PIJPERS A. , MELENDEZ R. , VULTO A. , VERHEIJDEN J. H. M.
Published: April 2008

Kadir, F., Zuidema, J., Pijpers, A., Melendez, R., Vulto, A. & Verheijden, J.H.M. Pharmacokinetics of intravenously, intramuscularly and intra‐adiposely administered carazolol in pigs. J. vet. Pharmacol. Therap. 13, 350–355.

The ß‐blocking agent carazolol is used for the prevention of stress syndromes in pigs. Little is known of the pharmacokinetics of this drug, and therefore of its residue status in meat. In this study carazolol pharmacokinetics were investigated in a randomized three‐way cross‐over design in five pigs. A dose of 0.025 mg/kg was given intravenously, intramuscularly and intra‐adiposely (in the subcutaneous fat layer). Carazolol was rapidly distributed and had a short half‐life of 1.2–4.2 h. The distribution volume was calculated to be 0.22‐0.65 1/kg. After intramuscular or intra‐adipose administration the absorption pattern was biphasic. A rapid initial phase was followed by a slow second phase. Absorption was found to be incomplete at 24 h after intramuscular and intra‐adipose administration ranging from 24 to 59% and 25 to 66%, respectively. The biphasic behaviour could be explained by retention of the drug in the tissues after absorption of the solvent was complete. A few hours after intravenous administration only negligible amounts of the drug were circulating in the body; however, considerable amounts of drug might have remained at the intramuscular or intra‐adipose injection site.

F. Kadir, Department of Pharmaceutics, University of Utrecht, Croesestraat 79, 3522 AD, Utrecht, The Netherlands.
Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba livia)
Authors: VANHAECKE E. , De BACKER P. , REMON J. P. , DEVRIESE L. A.
Published: April 2008

Vanhaecke, E., De Backer, P., Remon, J.P. & Devriese, L.A. Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba livia). J. vet. Pharmacol. Therap. 13, 356–360.

Tissue and plasma concentrations were determined after intravenous and oral administration of erythromycin to pigeons to establish the pharmacokinetics and bioavailability of the drug. A short mean half‐life of elimination of 0.9 h was found. The relative bioavailability after direct crop administration of erythromycin thiocyanate or erythromycin ethylsuccinate at a dosage rate of 100 mg/kg was less than 10%. At a drug concentration in drinking water of I g/I, erythromycin plasma levels were barely detectable, whilst lung and trachea concentrations reached a maximum of 1.6 μg/ml. Even after crop administration of 100‐mg/kg erythromycin thiocyanate, low plasma levels were obtained, whilst lung and trachea concentrations were substantially higher. Prescribed drinking‐water regimens seemed unable to yield therapeutic tissue concentrations. Only individual crop administration seemed an appropriate medication method. The use of erythromycin ethylsuccinate did not present any advantage in comparison with erythromycin thiocyanate.

J. P. Remon, Laboratory of Pharmaceutical Technology, Slate University of Ghent, Harelbekestraat 72, B‐9000 Ghent, Belgium.
Oral chloramphenicol in dwarf goats‐influence of vasopressin on its absorption and effect of diet on its biodegradation in ruminal fluid samples
Authors: NIJMEIJER S. M. , SAMURIWO E. , van DUIN C. T. M. , van MIERT A.S.J.P.A.M.
Published: April 2008

Nijmeijer, S.M., Samuriwo, E., van Duin, C.T.M. & van Miert, A.S.J.P.A.M. Oral chloramphenicol in dwarf goats‐influence of vasopressin on its absorption and effect of diet on its biodegradation in ruminal fluid samples. J. vet. Pharmacol. Therap. 13, 408–414.

The biodegradation of chloramphenicol was studied by incubating the drug (at concentrations of 72, 48 and 24 g/ml) with ruminal fluid samples from dwarf goats fed two different diets. Biodegradation of the drug was much faster in samples from animals which were fed with hay and concentrate than in those obtained from goats which were fed grass pellets only. Recently, it has been suggested that lysine‐vasopressin injected intravenously induces closure of the oesophageal groove in catde and goats. Therefore, the influence of lysine‐vasopressin on the oral absorption of chloramphenicol (50 mg/kg body wt) was studied in dwarf goats, using two formulations of chloramphenicol. The results suggest that vasopressin failed to induce this reflex mechanism. Furthermore, the shapes of the plasma concentration‐time curves after oral administration of chloramphenicol palmitate and chloramphenicol dissolved in propylene glycol were markedly different. Possible mechanisms for the observed differences are discussed.

S. M. Nijmeijer, Department of Veterinary Basic Sciences, Division PPPT, Faculty of Veterinary Medicine, PO Box 80.176, 3508 TD Utrecht, the Netherlands.
Thiamylal‐and halothane‐sparing effect of diazepam in dogs
Authors: III W. W. MUIR , BEDNARSKI L. , BEDNARSKI R.
Published: April 2008

The thiamylal‐and halothane‐sparing effect of diazepam was studied in two experiments using 32 conditioned dogs. Twenty‐four dogs received 0.05, 0.1 or 0.2 ml/kg diazepam or 0.9% saline (placebo) prior to the administration of thiamylal sodium i.v. Eight dogs received 0.1 or 0.2 mg/kg diazepam i.v. or placebo prior to or during halothane anesthesia. All three doses of diazepam significantly decreased the amount of thiamylal required to allow orotracheal intubation. The 0.2 mg/kg i.v. dose of diazepam produced the most significant effects. Premedication of dogs with diazepam did not reduce the concentration of halothane required to maintain anesthesia. The administration of 0.1 and 0.2 mg/kg diazepam i.v. during halothane anesthesia decreased the concentration of halothane required to maintain anesthesia. These studies demonstrate that diazepam reduces the amount of thiamylal required for orotracheal intubation, and when given intra‐operatively reduces the concentratíon of halothane required to maintain anesthesia.
Pharmacokinetics and elimination of salicylic acid in rabbits
Authors: SHORT C. R. , NEFF‐DAVIS C. A. , HSIEH L. C. , KORITZ G. D. , MALBROUGH M. S. , BARKER S. A. , DAVIS L. E.
Published: April 2008

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a V55of 0.249 ± 0.082 1/kg and cleared at a rate of 0.0432 ± 0.006 1/h/kg. The biological half‐life, calculated from the terminal disposition rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half‐life was eight to ten times longer than in the ruminants studied previously.
Plasma protein binding of nitroxynil in several species
Authors: ALVINERIE M. , FLOC'H R. , GALTIER P.
Published: April 2008

The binding of nitroxynil to total plasma proteins of cows, sheep and rabbits was characterized using equilibrium dialysis. The data indicate clearly that nitroxynil was highly (97‐98%) bound to plasma protein of each animal. This linear binding would be due to the particular power exerted by serum albumin.

The results are in good agreement with known pharmacokinetic properties of nitroxynil in domestic species.
Studies of meclofenamic acid and two metabolites in horses‐pharmacokinetics and effects on exercise tolerance
Authors: M. JOHANSSON I. , KALLINGS P. , HAMMARLUND‐UDENAES M.
Published: April 2008

The pharmacokinetics and the effects on treadmill exercise of the antiinflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two‐compartment open model. The average elimination half‐life was 1.4 h, the apparent volume of distribution 0.14 1/kg and the plasma clearance 0.12 1/h kg. Absorption was the rate‐limiting step after oral administration. Non‐compartmental analysis showed a mean absorption time of 4.3 h. The pharmacokinetics of two metabolites of meclofenamic acid were also studied in two of the horses. The elimination half‐lives of the two metabolites were virtually the same in each horse (3.0 h and 3.4 h). The blood lactate response to exercise was significantly decreased after treatment with meclofenamic acid, indicating a lower utilization of the glycolytic (‘anaerobic’) energy contribution during exercise. Circulatory capacity was apparently unaffected with an unchanged heart rate response to exercise.
Substance P: a neurogenic mediator of acute cellular inflammation in the dog?
Authors: THOMSEN M. KROGSGAARD
Published: April 2008

Substance P (SP) is a neuropeptide that has recently been implicated in the pathogenesis of neurogenic inflammation. SP has been shown to activate polymorphonuclear leukocytes (PMN) as well as other inflammatory cells. The present study investigated the direct stimulatory and priming effects of SP on canine PMN aggregation and migration. Direct stimulation of cell migration by SP was present at an unphysiologically high concentration of the mediator. However, when micromolar concentrations of SP were added to PMN prior to stimulation with sub‐optimal concentrations of leukotriene B4 (LTB4), the cells exhibited enhanced aggregation and migration, i.e. priming, when stimulated with the latter. Since SP has been reported to act via the formyl‐Met‐Leu‐Phe (fMLP) chemotaxin receptor, this mediator was also studied and found not to possess any effects similar to SP. Thus, the results indicate that SP acts as a primer of canine PMN functions in vitro via a receptor different from that for fMLP. Before ascribing SP a mediator role in canine neurogenic inflammation, in vivo studies determining the concentrations of, and responses to SP in inflamed tissue should be performed.
Pharmacokinetics of antipyrine and sulphadimidine (sulfamethazine) in camels, sheep and goats
Authors: ELSHEIKH H. A. , ALI B. H. , HOMEIDA A. M. , HASSAN T. , HAPKE H. J.
Published: April 2008

The pharmacokinetics of antipyrine and sulphadimidine were studied in male camels, sheep and goats. The two drugs were administered concomitantly. Following intravenous injection of antipyrine (25 mg/kg) and sulphadimidine (sulfamethazine) (100 mg/kg), the pharmacokinetics of the two drugs were adequately described by a one‐compartment model. Antipyrine half‐life in goats (2.58 h) was shorter than that in sheep (4.04 h) and camels (18.78 h). The plasma clearance was greatest in goats then sheep and then camels. For sulphadimidine, a significantly greater volume of distribution was observed in camels and the greatest plasma clearance and shortest half‐life were reported in goats. Sulphadimidine half‐life was 2.77 h in goats, 4.72 h in sheep and 7.36 h in camels. The present results suggest that goats have the fastest elimination of these drugs from the circulation, followed by sheep and then camels.
Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia
Authors: STEFFEY E. P. , WILLITS N. , WONG P. , HILDEBRAND S. V. , WHEAT J. D. , MEAGHER D. M. , HODGSON D. , PASCOE J. R. , HEATH R. B. , DUNLOP C.
Published: April 2008

Fifty‐eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P > 0.05) in die demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaC02 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91‐120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent.
The autoradiographic binding of [3H] quinuclidinyl benzilate to muscarinic receptors in the spinal cord of the sheep
Authors: BOUCHENAFA O. , LIVINGSTON A.
Published: April 2008

Autoradiography of [3H] quinuclidinyl benzilate was used to demonstrate the distribution of muscarinic acetylcholine binding in the spinal cord of sheep. Binding was confined to the grey matter of the cord, and was most densely distributed in the substantia gelatinosa region of the dorsal horn, the lamina X region around the central canal, the intermediolateral columns and in various regions of the ventral horn. The use of specific M/1 and M2 receptor subtype ligands, pirenzipine and 4‐DAMP indicated that both receptor subtypes were present in most regions of dense binding.
Distribution of oxytetracycline to tissue cages and granuloma pouches in calves and effect of acute inflammation on distribution to tissue cages
Authors: BENGTSSON B. , LUTHMAN J. , JACOBSSON S. O. , EKMAN S.
Published: April 2008

The effect of acute inflammation on oxytetracycline (OTC) distribution was studied in a tissue cage model in calves. An acute inflammatory reaction was induced in tissue cages by injecting lipopolysaccharide (LPS) fromSalmonella typhimurium. The distribution of OTC to tissue cage fluid (TCF) was also compared with distribution to fluid from granuloma pouches (GPF). Tissue from LPS‐injected cages showed histological changes indicating an acute inflammatory reaction. Concentrations of OTC were higher in LPS cages than in controls; at 1, 2, 4 and 10h the difference was statistically significant (P<0.05). Numerically the overall elimination rate constant(kel) was larger, elimination half‐life(t1/2) shorter, peak concentration(Cmax) higher, and time of peak concentration(Tmax) shorter in LPS cages than in controls. The area under the curve(AUC)of OTC was greater and the ratioAUCTCF/AUCserumwas higher in LPS cages than in controls. Although statistically significant differences were not found for all the pharmacokinetic parameters, it was concluded that distribution to and elimination from LPS cages were both faster than in controls. Concentration‐time profiles of OTC were similar in TCF and GPF in that concentrations were lower and elimination was more prolonged than in serum. Levels were higher in GPF than in TCF up to 3h after injection; thereafter the relationship was reversed. Distribution to and elimination processes from GPF appeared to be faster than from TCF as numericallykelwas higher,t1/2shorter andTmaxshorter in GPF than in TCF. It was concluded that the granuloma pouch model and the tissue cage model have similarities in distribution and elimination patterns and that differences are most probably due to differences in the ratio of the surface area to the volume.
On the construction of shortest confidence intervals and Bayesian highest posterior density intervals
Authors: GRIEVE A. P.
Published: April 2008

In this note it is argued that the principal characteristic of the confidence intervals proposed by Bartoszynski & Powers (1990) is not primarily the fact that they are of minimum length but that they are Bayesian highest posterior density intervals. A simple iterative process for determining the ends of the interval is presented.
The effect of ticlopidine on canine platelets, fibrinogen, and antithrombin III activity
Authors: BOUDREAUX M. K. , JEFFERS C. , LIPSCOMB D. , SPANO J. S.
Published: April 2008

The effect of ticlopidine on platelet function, platelet number, mean platelet volume, antithrombin III activity, and fibrinogen was evaluated in 10 laboratory beagles. Ticlopidine (62 mg/kg) significantly inhibited ADP‐ and collagen‐induced platelet aggregation within 2 days of the beginning of oral administration. Collagen‐induced platelet 14C‐serotonin release was not inhibited by day 9 of medication but was inhibited by day 20 in two of three beagles given medication for 32 days. Significant increases in mean platelet number were observed on days 2 and 5. The trend toward increased platelet number continued until day 16, at which time platelet number began to decrease toward baseline in three of three dogs treated for 32 days. Mean platelet volume (MPV) was significantly decreased compared to baseline on days 5 and 9. In three dogs treated for 32 clays, the lowest MPV was observed on day 9 in two dogs and on day 12 in one dog. Significant changes were not observed in antithrombin III activity or fibrinogen with ticlopicline treatment.
Pharmacokinetics of metoclopramide in goats
Authors: HUHN J. C. , KORITZ G. D. , NELSON D. R. , BROWN S. A.
Published: April 2008

The pharmacokinetics of a parenteral formulation of metoclopramide (mono‐chloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5‐mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min postdosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two‐compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half‐life of 0.62 h and a volume of distribution of the central compartment of 1.34 I/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post‐dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two‐compartment open model with first‐order absorption. The mean biological half‐life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5‐mgfkg dose administered by either route.