Journal of veterinary pharmacology and therapeutics.
Publisher:
Blackwell Scientific Publications.
Frequency: Bimonthly
Country: England
Language: English
Author(s):
American College of Veterinary Pharmacology & Therapeutics., Association for Veterinary Clinical Pharmacology and Therapeutics., European Association for Veterinary Pharmacology and Toxicology.
Start Year:1978 -
ISSN:
0140-7783 (Print)
1365-2885 (Electronic)
0140-7783 (Linking)
1365-2885 (Electronic)
0140-7783 (Linking)
Impact Factor
1.3
2022
| NLM ID: | 7910920 |
| (DNLM): | J41230000(s) |
| (OCoLC): | 04580359 |
| Coden: | JVPTD9 |
| Classification: | W1 JO97Q |
The effect of phenylbutazone on the plasma disposition of penicillin G in the horse. 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 ...
The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses. 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 fe...
Copper salicylate and copper phenylbutazone as topically applied anti-inflammatory agents in the rat and horse. Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as anti-inflammatory 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. Co...
Superoxide production by stimulated equine polymorphonuclear leukocytes–inhibition by anti-inflammatory drugs. Polymorphonuclear leukocytes (PMNLs) were isolated from an inflammatory exudate induced in the intercarpal joints of horses by an administration of carrageenin. Their superoxide production at rest and following stimulation with either serum-treated zymosan (STZ) or phorbol myristate acetate (PMA) was measured by cytochrome-c reduction. Stimulation of the cells increased the cytochrome-c reduction 10-15 times that of resting cells. The maxima were 20 nmol of reduced cytochrome-c per 10(6) cells per ml at 120 min (STZ) and 35 nmol of reduced cytochrome-c per 10(6) cells per ml at 60 min (PMA). T...
Pharmacokinetics of tinidazole in the horse. 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/...
Cardiovascular effects of detomidine, a new alpha 2-adrenoceptor agonist, in the conscious pony. The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post-injection. The magn...
Effect of calcium-channel blockers and salbutamol on the isolated mare uterus–interaction with the calcium agonist Bay K 8644. 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 a...
Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra). Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n = 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37 degrees C. Six-point Epi concentration-response (C-R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each...
Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse. 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 (lambda z), 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 +/- 0.0...
Cardiopulmonary effects of ephedrine in halothane-anesthetized horses. The cardiopulmonary effects of intravenous (i.v.) administration of the sympathomimetic drug ephedrine during two different levels of halothane anesthesia [end-tidal concentration of 1.37% (light anesthesia) and 2.1% (deep anesthesia)] were studied in eight horses. Anesthesia was induced and maintained using only halothane in O2. Ventilation was controlled to maintain a Paco2 of 38-42 mmHg. Following instrumentation and stabilization of the horse at the halothane concentration being studied, baseline measurements of cardiac output (Q), arterial blood pressure (AP), pulmonary artery pressure, h...
Absorption of two trimethoprim/sulphonamide combinations from the uterus of pony mares. 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 intra-uterine administration trimethoprim and sulphadiazine were detected in the milk of a lactating mare. In order to maintain plasma concentrations likel...
The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses. To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental ...
Pharmacokinetics and cardio-respiratory effects of oral theophylline in exercised horses. The pharmacokinetics of theophylline at rest and the effects on cardio-respiratory and blood lactate responses to exercise were investigated after repeated oral administrations in six healthy Standardbred horses. A dose of 5 mg/kg body weight was administered every 12 h. The binding of theophylline to plasma protein was also determined. There was good agreement between predicted and observed plasma concentrations of theophylline at steady state. The mean half-life of elimination was shown to be 17.0 +/- 2.5 h, the mean half life of absorption was 1.6 +/- 1.8 h, the apparent volume of distribut...
Characterization of a soft-tissue infection model in the horse and its response to intravenous cephapirin administration. A soft-tissue infection model was created in eight horses by infecting subcutaneous tissue chambers with Streptococcus zooepidemicus organisms. Responses of the horses to the infections were determined by monitoring changes in the complete blood count and body temperature and by following changes in the cytology and protein content of the tissue chambers. Systemic reactions to the infections included a mild neutrophilia, mild pyrexia and mild anemia. There was a marked influx of neutrophils and protein into the chambers after they were seeded with bacteria and chamber neutrophil viability decr...
Single-dose pharmacokinetics of detomidine in the horse and cow. The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 micrograms/kg) i.v. and i.m. doses. In addition, drug residues in some organs were determined. Concentrations were measured using a sensitive, detomidine-specific radio-immunoassay method. Rapid absorption following i.m. dosing occurred. Absorption half-lives were 0.15 h (horse) and 0.08 h (cattle). The mean peak concentration in the horse (51.3 ng/ml) was achieved in 0.5 h and in the cow (65.8 ng/ml) in 0.26 h. The areas under the concentration curve after i.m. dosing were 66...
ELISA detection of fentanyl in horse urine and plasma. The prototype of a commercial ELISA test kit designed for fentanyl determination in human urine has been evaluated for screening fentanyl in horse urine and plasma. The measurement of fentanyl after intravenous (2 mg) and intramuscular (0.25 mg) administration in undiluted plasma was not reproducible while accurate quantification of fentanyl in urine greatly depends on the composition of the horse urine. The ELISA assay, however, is simple and could be successfully used for quantitative measurements in diluted urine and for rapid qualitative screening for fentanyl in large numbers of urine sam...
Biphasic disruption of fasting equine gut motility by dopamine–a preliminary study. Dopamine was infused intravenously (1, 5 and 10 micrograms/kg/min) for 60 min in three fasted ponies. A dose-dependent increase in heart rate occurred that was rapid in onset and termination at the start and end of the infusions, respectively. Dose-dependent changes in gastric and small intestinal motility were observed. An initial marked inhibition of gastric contraction amplitude was followed by a secondary prolonged period of activity. At the same time the small intestine showed a prolonged period of irregular activity (phase II) and a marked increase in the interval between successive phas...
Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo-caeco-colonic junction. 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 pil...
Actions of the novel gastrointestinal prokinetic agent cisapride on equine bowel motility. 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 a...
Concentrations of immunoreactive leukotriene B4 in uterine lavage fluid from mares with experimentally induced and naturally occurring endometritis. Acute endometritis was induced in ovariectomized pony mares by infusion of a 1% solution of oyster glycogen. Maximum concentrations of immunoreactive leukotriene B4 in uterine washings coincided with the greatest rate of infiltration of neutrophils into the uterine lumen. Concentrations of immunoreactive leukotriene B4 decreased to basal levels 6 h after infusion and were unaffected by administration of ovarian steroids to ovariectomized mares. Uterine washings from mares with persistent endometritis did not contain significantly different concentrations of leukotriene B4 from genitally normal...
The effect of various antibacterial preparations on the in vitro morphology and chemotactic response of equine neutrophils. Two independent assay systems were used to study the effect of three antibacterial preparations on in vitro morphology and chemotaxis of equine neutrophils. Incubation of neutrophils with high (200 micrograms/ml) and medium (20 micrograms/ml) concentrations of neomycin impaired their response to standard chemoattractants. Trimethoprim/sulfadoxine (0.4/2.0 micrograms/ml-40/200 micrograms/ml) and benzylpenicillin (0.25-25 micrograms/ml) had no effect. Neutrophils collected from geldings 2 and 24 h after neomycin (5 mg/kg) administration had impaired responses to standard chemoattractants. Benzyl...
Development of a novel in vitro equine anthelmintic assay. An in vitro assay involving the use of a horse strongyle (Strongylus edentatus) and the micromotility meter has been developed to test for equine anthelmintic activity. Three commercially available equine anthelmintics (dichlorvos, ivermectin, and pyrantel pamoate) and an investigational drug (p-toluoyl chloride phenylhydrazone) were evaluated in this assay at four concentrations. After a 24-h incubation, greater than or equal to 10 micrograms/ml of all four drug treatments significantly (P less than or equal to 0.05) reduced the motility of ensheathed L-3 S. edentatus larvae, thereby indicati...
Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses. Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 +/- 0.016 (mean +/- SD) units o...
Pharmacokinetics of ticarcillin and clavulanic acid given in combination to adult horses by intravenous and intramuscular routes. The pharmacokinetics of ticarcillin and clavulanic acid following administration by the intravenous (i.v.) and intramuscular (i.m.) routes were investigated in six normal adult horses. Following i.v. administration, the ticarcillin disposition data conformed to a two-compartment model with an elimination half-life of 1.0 h. The disposition of clavulanic acid was described by a one-compartment model with an elimination half-life of 0.40 h. Following i.m. administration, the half-lives of both drugs were prolonged (ticarcillin 1.8 h, clavulanic acid 1.2 h). The bioavailability of ticarcillin was...