Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Brown MP, Gronwall R, Kroll WR, Beal C.Five foals from two to three days old were given a single oral dose of ampicillin trihydrate (20 mg/kg bodyweight [bwt]). Serum ampicillin concentrations were measured serially over a 24 h period. The study was repeated in the same foals at 16 to 21 days old. The mean peak serum ampicillin concentration at two to three days old was 5.0 micrograms/ml at 1 h after treatment; the mean peak serum concentration at 16 to 21 days old was 2.7 micrograms/ml at 2 h. The concentrations steadily declined and ampicillin was not detected in the serum from any of the foals by 24 h. Serum clearance averaged 1...
Baggot JD, Short CR.Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition (ie, distribution, metabolism and excretion) processes during the neonatal period. These alterations affect the plasma concentrations as well as the concentrations of drug attained at the receptor site. Some characteristics of the neonatal period include greater absorption from the gastrointestinal tract, lower extent of plasma protein binding, increased apparent volume of distribution of drugs that distribute in extracellular fluid or total body water, increased permeabil...
Kitzman JV, Wilson RC, Booth NH, Hendricks HL, Bush PB.The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volu...
Sullins KE, Messer NT, Nelson L.Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against...
Bijman J, Quinton PM.Single equine sweat glands were found to secrete for more than 1 h in vitro in response to pharmacologic secretagogues. The adrenergic agonists epinephrine and norepinephrine evoked maximal sweat rates of 2.0 nl X gland-1 X min-1. However, the concentration of norepinephrine (10(-5) M) required to evoke the maximal response was 10 times higher than that for epinephrine. Maximal sweat rates also were stimulated with the beta 2-adrenergic agonist terbutaline. This stimulation was blocked by the beta-adrenergic antagonist propranolol. Moderate sweating responses were also obtained with the alpha-...
Brown MP, Kelly RH, Gronwall RR, Stover SM.Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloram...
Nolan AM, Hall LW.The effects of four intravenous combinations, xylazine (0.7 mg/kg)/methadone (0.1 mg/kg), xylazine (0.7 mg/kg)/buprenorphine (0.004 and 0.006 mg/kg) and acepromazine (0.05 mg/kg)/buprenorphine (0.006 mg/kg) on arterial blood pressure, central venous pressure, heart rate, respiratory rate and blood gases were studied in four experimental ponies. With xylazine/buprenorphine and xylazine/methadone onset of sedation was rapid and obvious and although no surgical or diagnostic procedures were carried out, sedation was judged to be satisfactory for the next 30 to 40 minutes. Onset of sedation after ...
Duncan SG, Meyers KM, Reed SM.This study was designed to test the efficacy of heparin anticoagulant therapy in the horse and its effect on the formed elements of blood. Nine clinically normal, nontraumatized adult horses were subjected to 4 different heparin maintenance regimens (dosages of 320, 240, 160, and 40 U/kg of body weight). Porcine intestinal mucosa heparin (20,000 U/ml) was injected subcutaneously every 12 hours for 96 hours (total 9 times). A loading dose of one-third the maintenance dose was given IV just before the first heparin injection. Three control horses were given an equivalent volume of 0.9% saline so...
Kowalski KA, McConnell LA, Sadoff DA, Leid RW.Equine platelets, when treated with the anthelmintic drug diethylcarbamazine (DEC), gave a dose-dependent release of radiolabeled serotonin without concomitant aggregation. At levels of the drug that gave only minimal release of radiolabel, marked dose-dependent inhibition of platelet aggregation to three of four platelet agonists tested--adenosine diphosphate (ADP), collagen, and arachidonic acid--was observed. With ADP, inhibition was observed to be reversed by removal of DEC prior to agonist challenge. However, with collagen, inhibition was only partially reduced by prior removal of DEC; wh...
Robertson JT, Muir WW.A xylazine and butorphanol drug combination produced minimal and transient hemodynamic effects and no significant respiratory depression when administered to 6 healthy horses. Combining xylazine and butorphanol produced a synergistic analgesic effect and provided good chemical restraint for a standing surgical procedure.
Johnstone IB.Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M signific...
Brown MP, Kelly RH, Stover SM, Gronwall R.Six healthy adult mares were given a single IV injection of trimethoprim (TMP)-sulfadiazine (SDZ) at a dosage rate of 2.5 mg of TMP/kg of body weight and 12.5 mg of SDZ/kg. Serum, synovial, peritoneal, and urine TMP-SDZ concentrations were measured serially over a 48-hour period. The highest measured mean concentrations of TMP and SDZ were found in the first (0.5 hour) sample of serum, synovial fluid, and peritoneal fluid. The mean peak concentrations of TMP and SDZ averaged 4.37 micrograms/ml and 21.81 micrograms/ml for serum, 2.95 micrograms/ml and 15.31 micrograms/ml for synovial fluid, and...
Igwe OJ, Blake JW.The disposition kinetics of pemoline after iv and oral administration of 2.4 mg/kg of the drug were studied. The elimination half-life was 39.4 hr. The mean volume of distribution was 1.5 liters/kg indicating extensive tissue distribution and sequestration for an amphoteric drug. Plasma protein binding determined by in vitro equilibrium dialysis was concentration dependent. The mean binding capacity was found to be 0.80 mu-mol/g, an apparent dissociation constant of 3.73 X 10(-5) molar, and a total plasma protein concentration of 64.7 g/liter. The mean systemic availability by oral administrat...
Brimijoin S, Mintz KP, Prendergast FG.Interactions between dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA) and the cholinesterases were examined by the techniques of enzyme kinetics and fluorescence spectroscopy. When tested with partially purified enzyme preparations, DAPA was a potent inhibitor of butyrylcholinesterase (IC50 = 2 x 10(-7) M) but not of acetylcholinesterase (IC50 = 4 x 10(-4) M). For a detailed study of the effects of DAPA on butyrylcholinesterase (BuChE), the enzyme was purified to homogeneity from horse serum, with the aid of affinity chromatography on N-methyl acridinium. The kinetics of the inhibition o...
Katano Y, Imai S.The effects of dipyridamole on thromboxane A2 formation by horse platelet microsomes were studied in comparison with those of imidazole, a prototype inhibitor of TXA2 synthetase and nifedipine, a calcium antagonistic vasodilator. Thromboxane A2 was synthesized by incubating PGH2 with horse platelet microsomes and was assayed on the superfused rabbit aorta. Dipyridamole induced as strong an inhibition of TXA2 synthesis as imidazole, while nifedipine was without effects. The possible beneficial clinical outcomes of this effect of dipyridamole are discussed.
Brightman AH, Manning JP, Benson GJ, Musselman EE.Schirmer I tear tests were conducted on 14 horses. The test was performed before and after IV administration of xylazine hydrochloride, during maintenance anesthesia with halothane in oxygen, and 3 hours after discontinuation of anesthesia. Xylazine hydrochloride did not decrease tear production from the mean base-line value of 23.94 +/- 5.23 mm/min after its IV administration. Tear production was decreased to mean values of 15.57 +/- 4.29 mm/min at 30 minutes and 13.84 +/- 4.25 mm/min at 60 minutes during the maintenance of halothane anesthesia. Three hours after anesthesia was discontinued, ...
Lyons ET, Tolliver SC, Drudge JH.Seven critical tests in equids were conducted with single doses of fenbendazole (5 mg kg-1) alone (Panacur--American Hoechst, Somerville, NJ); (2 tests with paste and 1 with suspension formulation) or in combination with piperazine (American Hoechst); (40 mg base kg-1); (4 tests with paste formulation). The main purpose of the tests was evaluation of activity against benzimidazole-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus). Natural infections of 2 populations of benzimidazole-resis...
Love DN, Rose RJ, Martin IC, Bailey M.Twelve geldings were used to evaluate serum levels of penicillin following the intravenous (iv) and intramuscular (im) injection of benzylpenicillin, im procaine penicillin and im fortified benzathine penicillin, at a variety of dose rates. Blood samples were collected up to 7 h after iv and im benzylpenicillin, up to benzathine penicillin. Results were analysed using an analysis of variance and regression analyses were used to calculate the time taken for the serum penicillin concentration to decline to 0.5 micrograms/ml. As a result of the experiments the following dosage regimes could be re...
Morris DD, Fregin GF.Seventy-seven horses with atrial fibrillation (AF) were treated orally with quinidine sulfate (QS) at the University of Pennsylvania, School of Veterinary Medicine, Thirty-seven horses (48%) had adverse reactions to QS, the most common of which were nasal mucosal edema, anorexia, colic, and diarrhea. The mean highest daily QS dose was slightly greater in horses showing toxicity (P less than 0.1) and their conversion rate was less (P less than 0.05). A schedule of gradually increasing QS dose was time consuming, costly and not associated with fewer adverse reactions. Horses were compared by the...
Muir WW, Sams RA, Huffman RH, Noonan JS.The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted ...
Brown MP, Stover SM, Kelly RH, Farver TB.Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 micrograms/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 micrograms/ml and 3.92 micrograms/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and w...
Campbell WC.The avermectins are macrocyclic lactones produced by Streptomyces avermitilis. One of them has been chemically modified and given the non-proprietary name ivermectin. The compounds have shown efficacy against various stages of filarial parasites. With respect to pre-adult stages in the mammalian host, activity has been observed against Dirofilaria immitis in ferrets and dogs, and Dipetalonema viteae and Litomosoides carinii in jirds (Meriones); but activity has not been observed against the developing stages of Brugia spp. in jirds or Onchocerca spp. in cattle. The compounds have not shown act...
Skrabalak DS, Maylin GA.Dexamethasone and a metabolite, 9-fluoro-16α-methyl-6β, 11β, 16β-trihydroxy-1, 4-androstadiene-3, 17-dione, were detected in the urine of horses injected parenterally with the parent drug. The structure of the metabolite was elucidated by thin-layer chromatography, infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy.
Brown MP, Stover SM, Kelly RH, Farver TB.Six adult mares were given a single dose of ampicillin trihydrate (250 mg/ml) intramuscularly at a dosage of 20 mg/kg body weight. Serum, synovial fluid, peritoneal fluid and urine ampicillin concentrations were measured serially over a 48 h period. The mean peak serum ampicillin concentration was 2.49 micrograms/ml at 6 h. Ampicillin was found in synovial fluid and peritoneal fluid, which obtained mean peak ampicillin concentrations of 1.65 micrograms/ml and 1.81 micrograms/ml at 6 h and 4 h respectively. These concentrations declined in parallel with serum concentrations and were still detec...
Brown MP, Stover SM, Kelly RH, Farver TB.Six healthy adult mares were given a single dose of kanamycin sulfate (200 mg/ml) IM at a dosage rate of 5 mg/kg of body weight. Kanamycin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum kanamycin concentration was 12.55 microgram/ml at 1 hour. Mean peak kanamycin concentrations in synovial fluid and peritoneal fluid were 7.25 microgram/ml and 9.27 microgram/ml at 2 hours and 3 hours, respectively. These concentrations decreased steadily in parallel with serum concentrations and were still measurable at 48 h...
Kutter AP, Bettschart-Wolfensberger R, Schwarzwald CC, Portier KG, Ringer SK.To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses. Methods: Prospective, experimental trial. Methods: Nine adult horses weighing a median (range) of 535 (470-602) kg. Methods: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar pl...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
Freeman DE, Inoue OJ, Eurell TE.To study the effect of flunixin meglumine on short circuit current (Isc) in equine right ventral colon in vitro. Methods: Intestinal mucosa from healthy horses and ponies. Methods: Isc was measured in mucosa from the right ventral colon mounted in Ussing chambers. In experiment 1, collection and incubation solutions were: control (no additions); flunixin meglumine, 4 micrograms/ml; indomethacin, 10(-6) M; and flunixin meglumine (4 micrograms/ml) with 10(-6) M prostaglandin E2. In experiment 2, incubation conditions were: control [plain Krebs-Ringer bicarbonate [KRB] solution]; flunixin meglumi...
Nichols CL, Doherty TJ, Schumacher J, Jones PD, Sun X.To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone. Methods: 8 mares with no signs of lameness. Methods: In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexme...
Brotherton HO, Yost RA.A screening and confirmation procedure for drugs and metabolites in the blood serum and urine of racing animals was developed. Equine blood serum was spiked with low concentrations of several drugs of interest. Canine blood serum and urine were collected following oral doses of diethylcarbamazine, procaine, and phenylbutazone. Serum, urine, and extracts of each were analyzed, using a triple quadrupole mass spectrometer. Simultaneous screening of up to 50 drugs was possible in a single sample, in less than 2 minutes. Detection limits for most compounds were in the ng/ml to microgram/ml range, u...
Tobin T, Blake JW, Tai CY, Arnett S.Rapid intravenous injection of 1 g of procaine hydrochloride in Thoroughbred mares produced variable signs of central nervous system excitation for as long as 4 minutes. Plasma concentrations of procaine were similarly variable and transient, decreasing with a half-life of approximately 25 minutes. In vitro, plasma from freshly collected equine blood hydrolyzed procaine with a half-life of approximately 7.5 minutes. This hydrolysis was apparently due to plasma esterases. Penicillin, when added free or complexed as procaine-penicillin, did not protect procaine against hydrolysis by these plasma...
Zertuche JM, Brown MP, Gronwall R, Merritt K.Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with ...
Camargo FC, Robinson NE, Dirikolu L, Berney C, Eberhart S, Derksen FJ, Lehner AF, May J, Hughes C, Tobin T.Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, DeTolve P, Derksen FJ, Harkins JD, Lehner AF, Tobin T.Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. Objective: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural...
Beech J, Kohn C, Leitch M, Weinstein AJ, Gallagher M.Serum, synovial fluid, and urine concentrations of gentamicin were measured in normal mature horses which had been given a single dose of the drug. Mean peak serum concentration (16.8 microgram/ml) occurred in horses 30 minutes after they were given a single intramuscular dose of 4.4 mg of gentamicin/kg of body weight. In horses given a smaller dose of gentamicin (1.7 mg/kg), mean peak serum concentrations of gentamicin (10.2 microgram/ml) appeared at 1 hour. Synovial fluid concentration was maximum at 2 hours for both doses; in horses given the larger dose, mean peak concentration was 6.4 mic...
Barton AK, Gehlen H.The term remodeling describes the process resulting in a tissue that is structurally and architecturally altered compared to its healthy counterpart. At least in severe equine asthma, this occurs mainly, but not exclusively, as a consequence of neutrophilic airway inflammation and is characterized by hypertrophy of the smooth muscle layers in airway and arterial walls as well as fibrosis of the bronchial walls and pulmonary interstitial tissue. To date, much less is known for mild to moderate equine asthma. For a long time it was assumed that these processes are irreversible, and at least for ...
Schellenberg LM, Regenthal R, Abraham G.The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
Baggot JD, Love DN, Rose RJ, Raus R.The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (+/- sd) peak serum concentration of 23.2 +/- 10.2 micrograms/ml present at 30 mins, and at 8 h the serum concentration was 2.8 +/- 0.8...
Marr K, Marsh K, Hernandez L, Cunningham FM, Lees P.Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, possess properties consistent with their involvement in a range of inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily) was absorbed from the gastrointestinal tract, and penetrated readily into tissue cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6). Ionophore-stimulated leukotriene (LT) B4 synthes...
Rauws AG, van Schothorst M, Frik JF.The protein binding, the plasma half-life and the residue depletion of sulfamonomethoxine (SMM) after intramuscular administration were investigated in pigs, horses and cattle. Protein binding was weakly concentration-dependent. The bound fraction in plasma in the therapeutic range amounted to approximately 45, 40 and 50% for pigs, horses and cattle respectively, and the plasma half-lives were approximately 5.1, 5.7 and 3.1 hours respectively. SMM levels were less than 1 mug/g in muscle tissue after 36, 20 and 12 hours in pigs, horses and cattle respectively. In the kidney SMM levels were not ...
Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK.Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Duvivier DH, Votion D, Vandenput S, Art T, Lekeux P.Development of dry powder inhalation (DPI) for horses requires the use of an adapted face mask. In experiment I, 4 masks (A, B, C and D) were tested and factors influencing the delivery of the dry powder were determined. Mask A was one which is commercially available for metered-dose inhalation. Mask B had the same shape as Mask A but an airtight rubber seal was added for the connection between the mask and horse's head. Mask C was a prototype adapted for DPI with connection for the DPI device between the nostrils, airtight expiratory valves in front of each nostril and airtight rubber seal to...
LeBlanc M, Neuwirth L, Mauragis D, Klapstein E, Tran T.The effects of oxytocin on the percentage of technetium 99m albumin colloid (99mTc-microAA), cleared from the uterine lumen was measured in 13 mares. Scintigraphy was performed during 4 consecutive oestrous cycles, on Day 3 of oestrus during Cycles one and 3 and 48 h after ovulation during Cycles 2 and 4. Oxytocin (20 iu) was given i.v. after the initial scintigraphy image during Cycles 3 and 4. Seven multiparous mares (Group 1) were classified as 'susceptible' and 6 mares (2 nulliparous and 4 multiparous; Group 2) were classified as 'resistant' to endometritis. All mares cleared > 90% of 9...
Sarasola P, McKellar QA.The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
Velasco-Murillo V.It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug admi...
Gupta T, Chatterjee A.Pregnant mare's serum gonadotropin (PMSG) of 10 IU on day 5 of pregnancy induced luteal demise and consequently an absolute resorption of fetuses and placentae resulted on day 16 of pregnancy. Simultaneous regimen of PMSG and indomethacin or cortisone was found to be consistently effective in preventing the luteolytic effect of PMSG. The growth of the fetuses, placentae as well as corpora lutea was found to be parallel to controls. Similarly, shortening of the duration of pseudopregnancy to 10--12 days in the bilaterally hysterectomized rat by PMSG and its retaining the normal duration of 18--...
Cohen ND, Chu KK, Stanley SD, Wang N.To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. Methods: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis ...
Knych HK, Stanley SD, McKemie DS, Arthur RM, Bondesson U, Hedeland M, Thevis M, Kass PH.Although developed as a therapeutic medication, meldonium has found widespread use in human sports and was recently added to the World Anti-Doping Agency's list of prohibited substances. Its reported abuse potential in human sports has led to concern by regulatory authorities about the possible misuse of meldonium in equine athletics. The potential abuse in equine athletes along with the limited data available regarding the pharmacokinetics and pharmacodynamics of meldonium in horses necessitates further study. Eight exercised adult thoroughbred horses received a single oral dose of 3.5, 7.1, ...
Brown MP, Kelly RH, Gronwall RR, Stover SM.Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloram...
Kolm G, Gemeiner M, Deichsel K, Budik S, Aurich J, Aurich C.The failure of clearance mechanisms in the mare's uterus results in persistent inflammation and is considered a major cause of subfertility. Eighteen mares, of which three were susceptible to endometritis and four had been ovariectomised, underwent charcoal clearance testing to evaluate their clearance mechanisms. This consisted of installing 500 mg of charcoal (particle size 4 to 90 microm) added to 50 ml of phosphate-buffered saline (PBS) into the uterus. Forty-eight hours later the uterus was flushed out with 0.0012 per cent methylene blue in 50 ml of PBS for determination of the diluting f...
Zerpa H, Bailey SR, Berhane Y, Elliott J.Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been implicated in a number of conditions, such as acute equine laminitis, and are therapeutic targets for the treatment of this condition. Digital veins, rather than arteries, were investigated in the present study because they have been specifically implicated in the pathophysiology of acute laminitis. The order of potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists was determined in isolated rings of EDVs under ...
Chapman DI, Moss MS, Tomlinson PW, Harrison MP, Simmons PJ.1. Following single intramuscular doses of [14C]fluprostenol (0.5--2.4 micrograms/kg) to three female horses and to three gelded male horses, radioactivity was present in the plasma within 5 min; peak concn. (0.32--1.30 ng/ml fluprostenol equiv.) occurred 5 to 90 min after injection. Radioactivity was still present in the plasma of the females after three days. About 88% of fluprostenol is bound to plasma proteins. 2. Radioactivity was present in the parotid saliva of the gelded male horses within 10 min. Peak concn. (45--91 pg/ml fluprostenol equiv.) occurred from 5 min to 1 h after injection...
Anfossi P, Villa R, Montesissa C, Carli S.Lysine salts are often used in human pharmaceuticals to increase the solubility and absorption of acidic drugs when these are administered parenterally. In this study the intramuscular bioavailability of ketoprofen administered as the lysine salt was evaluated in horses (n = 5) treated intravenously and intramuscularly (2.2 mg/kg active substance) in a cross-over study. The absorption rate of ketoprofen administered as the lysine salt was rather low: the mean residence time increased from 31.7 min after IV injection to 128.9 min (after IM injection), and the bioavailability was high (mean 92.4...
Gleed RD, Dobson A.In horses in dorsal recumbency, spontaneously breathing oxygen, with halothane at a constant end-tidal concentration, the arterial oxygen tension (PO2) increased from 9.9 +/- 0.3 SEM kPa to 21.7 +/- 4.0 kPa with 0.8 micrograms kg-1 clenbuterol and to 29.1 +/- 3.8 kPa with 2.4 micrograms kg-1 clenbuterol. In horses initially in dorsal recumbency then turned to sternal recumbency the PaO2 rose to 54.0 +/- 3.0 kPa, but this rise was unaffected by clenbuterol administration. The response in dorsal recumbency was consistent with clenbuterol counteracting the factor postulated to direct the pulmonar...
Kovár J, Dürrová E, Skurský L.The interactions of three groups of probes (berberine alkaloids, tricyclic psychopharmaca and acridine derivatives) with isoenzymes of horse liver alcohol dehydrogenase and with rat liver alcohol dehydrogenase have been examined. These compounds inhibit the activity of the EE isoenzyme of horse liver alcohol dehydrogenase but differ in their behaviour towards the steroid-active enzymes (i.e. the ES isoenzyme of horse liver alcohol dehydrognase and alcohol dehydrogenase from rat liver): psychopharmaca inhibit, acridines activate and berberines do not bind. The ligands differ also in their influ...
