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.
Semrad SD, Hardee GE, Hardee MM, Moore JN.The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
Stover SM, Pool RR.Gentamicin sulfate (3 ml; 50 mg/ml) was administered intra-articularly into 30 normal equine radiocarpal joints after arthrocentesis. Arthrocentesis alone was performed on 10 normal radiocarpal joints. Synovial fluid evaluations and gross and microscopic examinations were performed on synovial fluid and synovial membrane of designated joints at selected daily intervals over a period of 10 days. Synovial fluid from gentamicin-injected joints had greater turbidity, higher RBC and WBC counts, and higher refractive indices than did joints not injected with gentamicin. The largest increases develop...
Ayres JW, Pearson EG, Riebold TW, Chang SF.The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 h...
Costa G, Labadia A, Garcia-Sacristan A.The effects of verapamil, a calcium antagonist agent, were studied on smooth muscle preparations of the lower urinary tract of horses. Verapamil (2 X 10(-4) to 2 X 10(-8) M) relaxed the ureter, urethra and urinary bladder preparations contracted by potassium (127 mM), L-noradrenaline (2 X 10(-5) M), histamine (2 X 10(-5) M) and acetylcholine (2 X 10(-5) M). These results allow the conclusion that verapamil has a dose-dependent relaxing effect on smooth muscle of the lower urinary tract.
Muir WW, Robertson JT.The visceral analgesic, cardiorespiratory, and behavioral effects induced by xylazine, butorphanol, meperidine, and pentazocine were determined in 9 adult horses with colic. Colic was produced by inflating a balloon in the horses' cecum. Heart rate, respiratory rate, mean arterial blood pressure, and cardiac output increased after cecal balloon inflation. Xylazine and butorphanol decreased the hemodynamic response to cecal balloon inflation. Meperidine and pentazocine had minimal effects on the cardiorespiratory changes induced by cecal balloon inflation. Xylazine produced the most pronounced ...
Kelly AB, Steffey EP, McNeal D, Willits N.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.
Nouws JF, Vree TB, Baakman M, Driessens F, Smulders A, Holtkamp J.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...
Steffey EP, Kelly AB, Farver TB, Woliner MJ.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...
Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL.Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square...
Barsan WG, Hedges JR, Syverud SA, Dalsey WC.The treatment of cardiovascular collapse and anaphylactic shock is largely empiric. A simple animal model was developed to evaluate the hemodynamic alterations in anaphylaxis. Eight adult New Zealand white rabbits of both sexes were studied. All animals weighed 3.8 kg to 5.3 kg. Sensitization was accomplished with a 2-mL subcutaneous dose of horse serum followed in two days with a 2-mL intravenous (IV) dose. At least 14 days elapsed after the IV dose before a 1-mL challenge dose of horse serum was given. On the day of the challenge dose, a femoral arterial catheter, arterial temperature probe,...
Schelling CG, Klein LV.A double-blind comparison of carbonated lidocaine and lidocaine hydrochloride in caudal epidural anesthesia was performed in 8 horses. Among 5 horses with successfully paired bilateral caudal epidural blockades, no significant differences in onset time, duration, or sensory blockade were demonstrated. In the present study, carbonated lidocaine did not offer an advantage over the hydrochloride salt for caudal epidural anesthesia in the horse.
Hunt JM, Gerring EL.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...
Orsini JA, Soma LR, Rourke JE, Park M.The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 microgra...
Mirbahar KB, McDonell WN, Bignell W, Eyre P.Pulmonary function tests were performed in seven conscious, standing horses. Changes in pulmonary mechanics and ventilation volumes were measured after inhalation challenge with saline (baseline), histamine (1% w/v solution for 5 min) and carbachol (0.5% w/v solution for 3 min). Comparisons between baseline and posthistamine values revealed a significant (P less than 0.05) increase in nonelastic work of breathing (Wb), maximum change in transpulmonary pressure (max delta Ppl), and pulmonary resistance (RL), while dynamic compliance (Cdyn) decreased (P less than 0.05). Tripelennamine completely...
Vaala WE.Other therapeutic agents used in foals for specific diseases are discussed elsewhere. The marked effect of species, age, and degree of maturity on drug metabolism in the neonate reinforces the danger of interspecies extrapolation of pharmacology, the need for information specific for the foal, and the necessity for monitoring drug levels in the individual. Suggested antimicrobial doses are listed in Tables 3, 4, and 6. Recommended doses of anticonvulsants and sedatives are listed in Table 8 and in the article "Intensive Care of the Neonatal Foal." The following are recommendations for drug the...
Hubbell JA, Muir WW.The rate of rise of arterial partial pressure of carbon dioxide (PaCO2) was determined in 49 apneic halothane-anesthetized horses following controlled ventilation. Drugs given for induction of anesthesia did not affect the rapid rate of rise of PaCO2 during the first minute after controlled ventilation, the PaCO2 at 1 minute after controlled ventilation, or the PaCO2 at which spontaneous ventilation began. Horses given xylazine-ketamine for induction of anesthesia had a significantly (P less than 0.05) faster rate of rise of PaCO2 after 1 minute following controlled ventilation than did horses...
Swanson CR, Muir WW, Bednarski RM, Skarda RT, Hubbell JA.The hemodynamic changes induced by constant infusions of dopamine or dobutamine (each 3, 5, and 10 micrograms/kg/min) were observed in halothane-anesthetized horses. Left ventricular dp/dt and cardiac output were increased in horses given dobutamine at dosage of 3 micrograms/kg/min and in those given either of the drugs at dosages of 5 and 10 micrograms/kg/min. Concomitant increases in systemic arterial blood pressure occurred at lower infusion dosage rates of dobutamine than those of dopamine and were modulated by dosage-related changes in peripheral vascular resistance that were different be...
Drumev D.Stated is the use of promising therapeutic formulae that produce prophylactic, metaphylactic, and curative effects at lower input of labour and handling, inciting lower unrest with animals, belonging chiefly to the type of the so-called 'therapeutic systems'. Particular attention is paid to drugs for programmed, continuous, and checkable release of the active ingredients in compliance with what is needed at the time (sustained release forms)-type OROS (oral osmotic system), type 'liquid reservoir', type 'glass cylinders', tablets and boluses of higher relative weight, or multilayer and mosaic ...
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...
Kamerling SG, Dequick DJ, Weckman TJ, Sprinkle FP, Tobin T.The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine a...
Bogan JA, Galbraith A, Baxter P, Ali NM, Marriner SE.Phenylbutazone, sulphadiazine and trimethoprim were administered to three horses on two occasions, recently fed and unfed, and the effect of feeding on the pharmacokinetics of the three drugs assessed. The mean peak concentrations of phenylbutazone and trimethoprim were reduced by feeding by 34 and 75 per cent, respectively. The pharmacokinetics of sulphadiazine were not significantly affected.
Kociba GJ, Bayly WM, Milne DW, Wigton DH, Gabel AA, Muir WW.Two groups of 6 Standardbred horses each were used to study hemostatic functions at rest and after exercise with furosemide or a placebo. One group which was trained was given maximum exercise on the racetrack, and the other, a less-fit group, was given submaximum exercise on the treadmill. There was no difference in furosemide compared to placebo trial results in either group in coagulation screening tests, platelet concentration, or retention of platelets in a glass bead column. Increased fibrinogen concentration and enhanced platelet retention were associated with maximum exercise. Aggregat...
Errecalde JO, Button C, Baggot JD, Mulders MS.The pharmacokinetics and bioavailability of theophylline in horses were investigated following both intravenous and intragastric administration of aminophylline solutions at doses corresponding to 15 and 10 mg/kg theophylline base. A rapid distributive phase with a half-life of approximately 15-30 min was followed by a slower elimination half-life averaging 15-17 h. The apparent volume of distribution averaged 850-900 ml/kg. Theophylline, administered as aminophylline solution, was both rapidly and completely absorbed from the equine digestive tract. Based on the bioavailability and dispositio...
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...
Toutain PL, Brandon RA, de Pomyers H, Alvinerie M, Baggot JD.Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alc...
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...
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 >...
Swanson CR, Muir WW.The influence of pharmacologic enhancement of cardiac output on the alveolar-to-arterial oxygen tension (difference (P[A-a]O2), physiologic right-to-left shunt fraction (Qs/Qt), and physiologic dead space-to-tidal volume ratio (VD/VT) ws studied in halothane-anesthetized horses in left lateral, right lateral, and dorsal recumbencies. Adult horses were anesthetized, using xylazine (2.2 mg/kg, IM), guaifenesin (50 mg/kg, IV), thiamylal (4.4 mg/kg, IV), and halothane (1.5% to 2% inspired) in 100% O2. Mechanical ventilation was controlled to maintain arterial eucapnia (PaCO2) 35 to 45 mm of Hg) fo...
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...
Semrad SD, Hardee GE, Hardee MM, Moore JN.The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
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...
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...
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 ...
Minuto J, Bedenice D, Ceresia M, Zaghloul I, Böhlke M, Mazan MR.Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Unassigned: To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability. Unassigned: Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respirato...
Pellegrini-Masini A, Poppenga RH, Sweeney RW.An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K, Matsumoto K, Toutain PL, Bousquet-Melou A....First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Methods: Experimental study with single administration. Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six h...
Hanafi AL, Reed RA, Trenholme HN, Sakai DM, Ryan CA, Barletta M, Quandt JE, Knych HK.To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Methods: prospective, randomized, blinded, crossover trial. Methods: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were c...
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 99mT...
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...
de Grauw JC, van de Lest CH, van Weeren PR.Articular tissues are capable of producing a range of eicosanoid mediators, each of which has individual biological effects and may be affected by anti-inflammatory treatment. We set out to develop and evaluate a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) approach for the simultaneous analysis of multiple eicosanoid lipid mediators in equine synovial fluid (SF), and to illustrate its use for investigation of the in vivo effects of non-steroidal anti-inflammatory drug (NSAID) treatment. Methods: Synovial fluid samples were obtained from normal joints of 6 adult...
Oyarzun-Ampuero F, Vidal A, Concha M, Morales J, Orellana S, Moreno-Villoslada I.The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth fact...
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 ...
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...
Easton S, Pinchbeck GL, Bartley DJ, Hotchkiss E, Hodgkinson JE, Matthews JB.The aim of this study was to determine practices, attitudes and experiences of UK prescribers of anthelmintics for horses and livestock. A questionnaire was sent by direct email to groups licenced to prescribe these medicines. These were veterinarians, Suitably Qualified Persons (SQPs, registered with the Animal Medicines Training Regulatory Authority) and veterinary pharmacists. The survey was also advertised through social media. It comprised questions relating to demographics, training experiences, current prescribing practices, as well as personal opinions on anthelmintic selection, diagno...
