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 |
Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies. Single doses of sodium ampicillin (10 mg/kg) and kanamycin sulfate (5 mg/kg) were administered intramuscularly (i.m.) separately, and then together, to five pony mares. The plasma antibiotic concentration-time curves were constructed. The pharmacokinetic parameters of the antibiotics given separately were not altered by concurrent administration. Four of the five pony mares were then given the i.m. kanamycin/ampicillin combination 4 h after acute synovitis and fever had been induced by injection of lipopolysaccharide into the left intercarpal joint. The plasma concentration-time curves and the...
Colonic alpha 2-adrenoceptor-mediated responses in the pony. The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induc...
Pharmacological modulation of postprandial colonic motor activity in the pony. 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 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but w...
Evaluation of the potential for interference by dimethyl sulfoxide (DMSO) in drug detection in racing animals. Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfer...
A pharmacokinetic study of phenobarbital in mature horses after oral dosing. 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 (Clt/F) of phenobarbital were 0.753 +/- 0.115 l/kg and 27.9 +/- 9...
Cardiopulmonary function during 5 hours of constant-dose isoflurane in laterally recumbent, spontaneously breathing horses. Hemodynamic and respiratory effects of 5 h of unvarying 1.57%, end-tidal (1.2 MAC) isoflurane in O2 anesthesia were characterized in ten left laterally recumbent horses. Compared to base line values at 30 min of constant dose isoflurane, cardiac output, hematocrit, total plasma solids, PaCO2, and peak inspired gas flow progressively and significantly (P less than 0.05) increased over the course of study. Arterial blood pressure increased (P less than 0.05) during the first 2 h of constant dose of isoflurane then decreased and remained near base line values. Inspiratory time progressively decre...
Pharmacokinetics of dantrolene sodium in horses. 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 ...
Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses. The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of t...
Actions of non-steroidal anti-inflammatory drugs on equine leucocyte movement in vitro. The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indome...
Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses. Previous studies demonstrated that plasma clearance of organic anions such as bilirubin, bile acid, sulfobromophthalein (BSP) and indocyanine green (ICG), was reduced from 36% (bile acid) to 55% (ICG) in fasted (3 days) horses. It is believed that a general decline in carrier-mediated hepatic uptake may have accounted for those changes. However, fasting may also affect hepatic blood flow, thereby contributing to reduced clearance of these compounds. In order to test this hypothesis, plasma clearance of antipyrine, acetaminophen and lidocaine, drugs known to be cleared by the liver yet not susp...
The lack of effect of inoculation with equine influenza vaccine on theophylline pharmacokinetics in the horse. Several studies conducted during the past few years have shown that the pharmacokinetics of a variety of drugs may be altered following viral infection or vaccination. The elimination of drugs which are extensively metabolized, such as theophylline, may be prolonged, especially following exposure to RNA viruses such as Type A influenza or similar orthomyxoviruses. The purpose of this study was to determine whether vaccination of horses with equine influenza virus affected pharmacokinetic parameters describing the distribution and elimination of intravenously administered theophylline. Three th...
Pharmacokinetics and diuretic effect of bumetanide following intravenous and intramuscular administration to horses. Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailabi...
Phenylbutazone and oxyphenbutazone distribution into tissue fluids in the horse. The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean A...
Dermal reactivity to histamine, serotonin and bradykinin in relation to allergic skin reactions of the horse. The reactivity of horse skin to intradermal inoculation of histamine, serotonin and bradykinin was investigated, and the resulting reactions compared with those produced in the same horses by a 1% whole-body extract of Culicoides. Both histamine and bradykinin produced large reactions, but there was no significant correlation between the dermal responsiveness to insect allergen and either histamine or bradykinin. Two anti-histamine drugs (promethazine hydrochloride and tripelennamine hydrochloride) were effective in reducing the reaction produced by the insect extract.
Phenylbutazone in the horse: a review. Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies. The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-...
Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses. Phenylbutazone was administered to six Thoroughbred horses in a cross-over study in which the horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half-life of phenylbutazone did n...
Immediate and long-term effects of halothane anesthesia on equine platelet function. The acute and long-term quantitative and qualitative effects of halothane anesthesia on equine platelet performance were studied in fourteen horses. Horses were anesthetized with only halothane in O2 for about 8.0 MAC hours. Platelet numbers declined during the anesthetic period but returned to normal within 24 h. Platelet aggregation was significantly diminished during the anesthetic period and for up to 4 days after anesthesia. A period of hyperaggregability occurred at the 7th day.
Some dynamic and toxic effects of theophylline in horses. A single intravenous administration of theophylline as aminophylline at 10 mg/kg to four mares induced a diuresis in which maximal urine production was more than seven times the control volume. The diuretic effect was maximal within the first hour post-administration, and lasted approximately 6 h. Theophylline resulted in dose-related tachycardia, polypnoea and nervous symptoms (tactile, visual and auditory hypersensitivity, muscle tremor, sweating) in normal mares, but had only minor effects on arterial and central venous blood pressures, intrapleural pressure, red blood cell variables and pl...
Disposition of sulfadimidine and its N4-acetyl and hydroxy metabolites in horse plasma. The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/k...
Cardiovascular and respiratory effects of acetylpromazine and xylazine on halothane-anesthetized horses. 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 treatme...
Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity. Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study...
The effect of prostaglandin E1 on motility of the equine gut. Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the pr...
Phenylbutazone and its metabolites in plasma and urine of thoroughbred horses: population distributions and effects of urinary pH. A survey of plasma and urinary concentrations of phenylbutazone and its metabolites in thoroughbred horses racing in Kentucky was carried out. Post-race blood samples from more than 200 horses running at Latonia Racetrack and Keeneland in the Spring of 1983 were analysed. The modal plasma concentration of phenylbutazone was between 1 and 2 micrograms/ml, the mean concentration was 3.5 micrograms/ml and the range was up to 15 micrograms/ml. Oxyphenbutazone had a modal plasma concentration between 1 and 2 micrograms/ml, a mean concentration of 2.07 micrograms/ml and a range of up to 13 microgram...