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.
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...
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...
Kirschvink N, Art T, Lekeux P, Roberts C, Gustin P.8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic receptor agonist, U46619. Furthermore, the potential cap...
Jones DM, Fielden ED, Carr DH.Two intact and 2 ovariectomized mares aged 3-16 years had bipolar electrodes implanted in the myometrium to measure electromyographic (emg) activity during normal and exogenously simulated (with oestrogen and progesterone) cyclical activity (anoestrus, transition, oestrus and dioestrus). Oxytocin, cloprostenol, propantheline bromide and clenbuterol were administered during each cycle stage. In 1 mare, emg activity was recorded during natural breeding (4 times) and through the first 20 days of pregnancy. Simultaneous intrauterine pressure recordings (IUP) using an open tipped catheter system we...
Sinn D, Wintzer HJ.The pharmacokinetics of racemic phenprocoumon were studied in 8 adult horses after the single intravenous and oral administration of 0.75 mg/kg. After i.v. administration the plasma concentration of phenprocoumon showed a biphasic decline in time. The pharmacokinetics were calculated on the two-compartment open model. The average plasma half-life (beta-phase) was 22 hours, the apparent volume of distribution was 0.61 l/kg, Cltot was 25.2 ml/kg/h (13.9-40.9 ml/kg/h). The systemic bioavailability of oral phenprocoumon was 97.6%, Tmax was found to be 4-12 hours. The effect of phenprocoumon on the...
Campbell NB, Jones SL, Blikslager AT.A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l...
Steffey EP, Willits N, Wong P, Hildebrand SV, Wheat JD, Meagher DM, Hodgson D, Pascoe JR, Heath RB, Dunlop C.Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no...
Cook G, Papich MG, Roberts MC, Bowman KF.To determine the i.v. pharmacokinetics of cisapride and measure systemic absorption after rectal administration. Methods: 5 healthy adult mares (380 to 610 kg). Methods: Cisapride was administered, i.v., at a dosage of 0.1 mg/kg of body weight. In the same horses, after a 1-week washout period, cisapride was administered rectally at a dosage of 1 mg/kg by mixing crushed tablets with propylene glycol and administering the mixture into the rectum. After each drug administration, a series of blood samples were collected. Plasma was obtained and analyzed by high-performance liquid chromatography t...
Stover SM, Brown MP, Kelly RH, Farver TB.Six healthy adult mares were given a single dose (25 mg/kg of body weight) of sodium oxacillin IM. Oxacillin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum oxacillin concentration was 9.75 microgram/ml at 0.5 hour after injection. Mean peak oxacillin concentrations in synovial and peritoneal fluids were 1.45 microgram/ml and 2.60 microgram/ml at 1 hour and 2 hours, respectively. These concentrations decreased in parallel with serum values and were not measurable at 48 hours. Urine concentrations of oxacilli...
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 ...
Knych HK, Finno CJ, Baden R, Arthur RM, McKemie DS.The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of r...
Delbeke FT, Baert K, De Backer P.Urinary and plasma concentrations of the nonsteroidal anti-inflammatory drug tiaprofenic acid were determined following oral and intramuscular administration of a dose of 1 g to five fasted horses. Quantitation was performed by high-performance liquid chromatography (HPLC). The limit of quantitation (LOQ) was 0.1 microg/ml and 0.5 microg/ml in 2 ml plasma and 1 ml urine, respectively. Assay precision and extraction recovery were between acceptable values. Tiaprofenic acid pharmacokinetics were described by non-compartment analysis of the data. Absorption was faster after oral administration as...
We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM). PPF-induced relaxation was partially inhibited in the presence of L-NAME (a nitric oxide (NO) synthase inhibitor; 100 µM), ODQ (an inhibitor of...
Knych HK, Steffey EP, Stanley SD.To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Methods: Randomized crossover design. Methods: Nine healthy adult horses aged 9 ± 4 years and weighing of 561 ± 56 kg. Methods: Three dose regimens were employed in the current study. 1) 0.03 mg kg(-1) detomidine IV (D), 2) 0.2 mg kg(-1) yohimbine IV (Y) and 3) 0.03 mg kg(-1) detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1 week in between subsequent regimens. Blood samples were obtained and plasma analyzed f...
Soma LR, Uboh CE, Rudy JA, Smith MS.To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone. Methods: Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA. Methods: Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV. Results: Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-...
Langsetmo I, Weigle GE, Erickson HH, Fedde MR.Exercising horses have extremely high right and left atrial pressures. Limitation in ventricular function (i.e. relaxation) may play a role in these high pressures. We studied relaxation characteristics of the right ventricular myocardium and the impact of frusemide (2.0 mg/kg bwt i.v.) on these characteristics in horses exercising at 8, 10, 12 and 14 m/s. Exercise tests were performed 4 h after administration of frusemide. Right ventricular (RV) pressure was analysed using Fast Fourier Transform techniques to remove non cardiac components of the pressure signal. Mean right atrial (RA) pressur...
Wood T, Tai CL, Taylor DG, Woods WE, Wang CJ, Houtz PK, Tai HH, Weckman TJ, Yang JM, Sturma L.Detomidine is a potent non-narcotic sedative agent which is currently in the process of being approved for veterinary clinical use in the United States. Since no effective screening method in horses is available for detomidine, we have developed an 125I radioimmunoassay for detomidine in equine blood and urine as part of a panel of tests for illegal drugs in performance horses. Our 125I radioimmunoassay has an I-50 for detomidine of approximately 2 ng/ml. Our assay shows limited cross-reactivity with the pharmacodynamically similar xylazine, but does not cross-react with acepromazine, epinephr...
López-Sanromán J, Cruz J, Santos M, Mazzini R, Tabanera A, Tendillo FJ.The objective of this study was to determine the effects of the alkalinization on the local analgesic efficacy of 1% ketamine in the abaxial sesamoid nerve block in horses. Thirty-six mature healthy horses were randomly assigned to four groups for the following treatments; an abaxial sesamoid block with 5 mL of saline solution (control saline); an abaxial sesamoid block with 5 mL of a solution containing 1% ketamine (KETs 1%); an abaxial sesamoid block with 5 mL of a solution containing saline solution and 0.5 mEq of sodium bicarbonate (control bicarbonate); and an abaxial sesamoid block with ...
Cox S, Yarbrough J.A new method of analysis has been developed and validated for the determination of firocoxib, a new nonsteroidal anti-inflammatory drug (NSAID) approved for use in horses and dogs to control pain and inflammation associated with osteoarthritis. Following a liquid extraction using ethyl acetate:hexane (40:60), samples were separated by isocratic reversed-phase HPLC on a Sunfire C(18) column and quantified using UV detection at 290 nm. The mobile phase was a mixture of water with 0.025% trifluoroacetic acid and acetonitrile, with a flow-rate of 1.1 ml/min. The procedure produced a linear curve o...
Ross J, Dallap BL, Dolente BA, Sweeney RW.To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. Methods: 6 adult horses. Methods: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration ver...
Chu KK, Wang N, Stanley S, Cohen ND.The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulti...
Medina-Torres CE, Underwood C, Pollitt CC, Castro-Olivera EM, Hodson MP, Richardson DW, van Eps AW.A suitable method for evaluating lamellar perfusion changes and their metabolic consequences is currently lacking. Objective: To examine perfusion changes in lamellar tissue using serial microdialysis measurements of urea clearance and energy metabolites. Methods: Randomised, controlled (within subject) experimental trial. Methods: Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate and its clearance was used to estimate local perfusion. Samples were collected every 15 min fo...
Gehlen H, Groner U, Rohn K, Stadler P.In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamin...
Ekstrand C, Nostell K, Gehring R, Bondesson U, Bröjer J.Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentrati...
Baggot JD, Love DN, Stewart J, Raus J.The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (...
Galey FD, Beasley VR, Schaeffer DJ, Davis LE.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...
Knoll U, Strauhs P, Schusser G, Ungemach FR.Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5-aminosalicylic acid (5-ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by ...
Corveleyn S, Deprez P, Van der Weken G, Baeyens W, Remon JP.Six healthy mares ranging in age from 6 to 12 years and weighing from 415 to 540 kg were used to determine the rectal bioavailability of ketoprofen. For the rectal administration, three different formulations, each containing 1 g of ketoprofen, were administered in a fatty and a hydrophilic suppository base and as a liquid suspension. An average elimination half-life of 1.3 h (+/-1.2) was found. The average value for the total plasma clearance (ClT) was 131.9mL/ min.kg (range 95-183.5). The volume of distribution Vd(area) was 255 mL/kg and the mean residence time (MRT) value was 0.47 h. After ...
Ambrisko TD, Moens Y.In a previous in vitro study using saline medium, the authors showed that certain drugs changed the voltages of lithium dilution cardiac output (LiDCO) sensors and also influenced their accuracy in measuring lithium concentrations. These two parameters correlated and so we examined whether such drug-sensor interaction exists when LiDCO sensor was exposed to xylazine in blood. Methods: Five healthy adult warm-blood horses were injected with 0.5 mg kg(-1) xylazine i.v. Physiological saline solution and venous blood were consecutively sampled through the same LiDCO sensor at 60, 45, 30, 15, and 0...
Hunt JP, Haywood PE, Moss MS.A gas chromatographic screening procedure for the non-steroidal anti-inflammatory group of drugs is described. The method invovles on-column methylation of the carboxylic acid group using trimethylanilinium hydroxide as the methylating reagent. Fifteen such drugs were studied. Eight of these were detected in urine collected from horses that had received these compounds orally and for these drugs, rates of urinary excretion are recorded. Seven other members of this group of drugs were shown to be detectable by this procedure but in these cases the drug was added to urine and not administered to...
Knych HK, Steffey EP, Mitchell MM, Casbeer HC.The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals. The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages. Experimental study in healthy foals. Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood sam...
Eades SC, Moore JN.Changes in lateral cecal arterial blood flow, mean internal carotid arterial pressure, and heart rate caused by nasogastric administration of fenoldopam (3, 6, and 9 mg/kg of body weight), a selective agonist of dopaminergic receptors, were recorded in 7 healthy horses. Cecal arterial blood flow was significantly increased within 30 minutes after administration of fenoldopam at all 3 dosages, with the peak increases from baseline (67.8 +/- 17.5 ml/min) being 125 +/- 28, 120 +/- 22, and 153 +/- 32 ml/min for 3, 6, and 9 mg/kg, respectively. Although carotid arterial pressure did not change sign...
