Pharmacokinetics in horses involves the study of how drugs are absorbed, distributed, metabolized, and excreted in equine species. This field of study provides insights into the time course of drug concentrations within the horse's body and helps in understanding the effects of various pharmaceuticals. Key parameters in equine pharmacokinetics include absorption rates, bioavailability, half-life, and clearance. These parameters can vary significantly due to factors such as age, breed, and health status of the horse. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetic profiles of different drugs in horses, aiming to optimize dosing regimens and improve therapeutic outcomes in equine medicine.
Garré B, Baert K, Nauwynck H, Deprez P, De Backer P, Croubels S.The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF wer...
Hubbell JA, Sams RA, Schmall LM, Robertson JT, Hinchcliff KW, Muir WW.Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objective: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, h...
Dirikolu L, Karpiesiuk W, Lehner AF, Hughes C, Granstrom DE, Tobin T.Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of abs...
Meyer S, Giguère S, Rodriguez R, Zielinski RJ, Grover GS, Brown SA.The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six...
Larenza MP, Peterbauer C, Landoni MF, Levionnois OL, Schatzmann U, Spadavecchia C, Thormann W.To evaluate pharmacokinetics of ketamine and norketamine enantiomers after constant rate infusion (CRI) of a subanesthetic dose of racemic ketamine or S-ketamine in ponies. Methods: Five 6-year-old Shetland pony geldings that weighed between 101 and 152 kg. Methods: In a crossover study, each pony received a CRI of racemic ketamine (loading dose, 0.6 mg/kg; CRI, 0.02 mg/kg/min) and S-ketamine (loading dose, 0.3 mg/kg; CRI, 0.01 mg/kg/min), with a 1-month interval between treatments. Arterial blood samples were collected before and at 5, 15, 30, 45, and 60 minutes during drug administration and...
Grimsrud KN, Mama KR, Thomasy SM, Stanley SD.Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objective: To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase...
Nagy A, Bodo G, Dyson SJ, Szabo F, Barr AR.Proximal diffusion of local anaesthetic solution after perineural anaesthesia may lead to the desensitisation of structures other than those intended. However, there is no evidence-based study demonstrating the potential distribution and diffusion of local anaesthetic solution after perineural analgesia in the distal limb. Objective: To document the potential diffusion of local anaesthetic solution using a radiopaque contrast model and to evaluate the influence of walking compared with confinement in a stable after injection. Methods: Radiopaque contrast medium was injected subcutaneously over...
Cribb NC, Bouré LP, Hanna WJ, Akens MK, Mattson SE, Monteith GJ, Weese JS.To assess the antimicrobial elution characteristics, toxicity, and antimicrobial activity of amikacin-impregnated ferric-hyaluronate implants (AI-FeHAI) for amikacin delivery to the tarsocrural joint of horses. Methods: Experimental study. Methods: AI-FeHAI implants, equine cartilage, and synovium, and horses (n=6). Methods: In vitro study: Five AI-FeHAI were placed in saline solution with daily replacement until implant degradation. Eluent was tested for amikacin concentration and bioactivity. Synovial and cartilage explants were incubated in the presence or absence of AI-FeHAI for 72 hours a...
Nourian AR, Mills PC, Pollitt CC.Intraosseous (i.o.) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 microL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood sample...
Enderle AK, Levionnois OL, Kuhn M, Schatzmann U.To compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses. Methods: Prospective, randomized, blinded clinical trial. Methods: Forty horses (ASA I-III) undergoing elective surgery. Methods: Horses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI ...
You Y, Uboh CE, Soma LR, Guan F, Li X, Rudy JA, Liu Y, Chen J.An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method for fast-throughput analysis of eight anabolic and androgenic steroids (AAS) in equine plasma is reported. Analytes were recovered by liquid-liquid extraction using methyl tert-butyl ether, separated on a 1.9 microm C(18) reversed-phase column, and analyzed in positive electrospray ionization mode on a triple quadrupole mass spectrometer with selected reaction monitoring (SRM) and full product ion scans. Two SRM ion transitions were monitored for each AAS during screening to obtain highly selective screenin...
Capponi L, Schmitz A, Thormann W, Theurillat R, Mevissen M.To investigate cytochrome P450 (CYP) enzymes involved in metabolism of racemic and S-ketamine in various species and to evaluate metabolic interactions of other analgesics with ketamine. Methods: Human, equine, and canine liver microsomes. Methods: An analgesic was concurrently incubated with luminogenic substrates specific for CYP 3A4 or CYP 2C9 and liver microsomes. The luminescence signal was detected and compared with the signal for negative control samples. Ketamine and norketamine enantiomers were determined by use of capillary electrophoresis. Results: A concentration-dependent decrease...
Back W, MacAllister CG, van Heel MC, Pollmeier M, Hanson PD.Lameness is a highly prevalent condition in horses and the principal cause of removal from athletic activity. In clinical studies to evaluate nonsteroidal anti-inflammatory drug therapies, force plates are commonly used to assess improvement of lameness objectively. Objective: To use a force plate to determine the optimal dose of a new COX-2 inhibitor (firocoxib) that will reduce lameness, when administered orally to horses once daily. Methods: Sixty-four horses that exhibited chronic lameness presumed due to osteoarthritis, including navicular disease, in at least one of the frontlimbs and at...
Hustace JL, Firshman AM, Mata JE.To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. Methods: 4 adult horses. Methods: 6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography. Results: Mean +/- SD distribution half-life of metformin following IV administration was 24.9 +/- 0.4 minutes with a volume of distribution of 0.3 +/- 0.1 L/kg. Mean area under the curve was 20.9 +/- 2.0 h.microg/mL for IV adminis...
Shank BR, Ofner CM.Pergolide mesylate (proprietary name Permax) is used to treat equine Cushing's syndrome. Since pergolide mesylate has been removed from the market, the tablets are no longer available. Therefore, pergolide mesylate preparations have to be compounded for veterinary use. Compounded oral liquid formulations have been given arbitrary beyond-use dates of 14 days (aqueous) to 90 days (oil based). The goal of this study was to determine the stability of a 0.2 mg/mL pergolide oral liquid prepared according to a previousy published formulation and stored at room temperature. The sample preparation and ...
Sasaki N, Tsuzuki N, Yamada M, Minami T, Yamada H.This study aimed to establish a standard dose and sample collection time for (13)C phenylalanine and (13)C-Dipeptide breath test in horses. To evaluate dose-dependent effects, healthy horses received 2.5 mg/kg, 5 mg/kg, and 10 mg/kg (13)C phenylalanine dissolved in 1 ml/kg distilled water and 1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg (13)C dipeptide dissolved in 2 ml/ kg distilled water. Tmax was observed during the sample collection time. For (13)C phenylalanine, the standard deviation of Cmax at 5 mg/kg was lower than that of 10 mg/kg. For (13)C dipeptide, the standard deviation of Tmax was the low...
Haerdi-Landerer MC, Habermacher J, Wenger B, Suter MM, Steiner A.The search for an effective treatment for septic arthritis is ongoing. Current therapies are expensive since they require repeated joint lavage and long term antibiotic treatment. Local application of antimicrobial drugs is advantageous because high concentrations can be attained at the infection site, although repeated injections increase the risk of superinfection of the joint. Thus, slow release formulations, which have the advantage of local treatment yet single application of the drug, are appealing. Antibiotics used in slow release formulations are selected for tissue compatibility, an a...
Gargala G, Le Goff L, Ballet JJ, Favennec L, Stachulski AV, Rossignol JF.Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). The aim of this work was to document inhibitory activities of nitazoxanide (NTZ, [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide]) and new thiazolides/thiadiazolides on S. neurona in vitro development, and investigate their structure-activity relationships. S. neurona was grown in bovine turbinate cell cultures. At concentrations varying from 1.0 to 5.0mg/L, nitazoxanide and 21 of 32 second generation thiazolide/thiadiazolide agents exerted a > or =95% maximum inhibition on S. neuro...
Machnik M, Gerlach M, Kietzmann M, Niedorf F, Thevis M, Schenk I, Guddat S, Düe M, Schänzer W.The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid-liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
Barker SA.Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole. This study examines the urine concentrations of aminorex as a function of time following administration of synthetic, racemic aminorex. Confirmation of the presence of aminorex in urine samples from the horses known to be treated with levamisole is also presented as are data concerning the concentrat...
Elfenbein JR, Sanchez LC, Robertson SA, Cole CA, Sams R.To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations. Methods: Nonrandomized, experimental trial. Methods: Five adult horses, each with a permanent gastric cannula weighing 534 +/- 46 kg. Methods: Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose-to-ground (NTG) height was used as a measure of sed...
De Clercq D, van Loon G, Tavernier R, Verbesselt R, Deprez P.To investigate effects of IV administration of propafenone for naturally occurring and experimentally induced chronic atrial fibrillation in horses. Methods: 2 horses with naturally occurring atrial fibrillation and 4 horses with pacing-induced atrial fibrillation. Methods: Horses received a bolus of propafenone (2 mg/kg, IV over 15 minutes). If atrial fibrillation persisted after 20 minutes, a continuous infusion of propafenone (7 microg/kg/min) was given for 120 minutes. Before, during, and after treatment, plasma propafenone concentrations, hematologic and serum biochemical values, and elec...
Nourian AR, Mills PC, Pollitt CC.Microdialysis (MD) was used for continuous monitoring of the lamellar extracellular fluid (ECF) in six mature healthy Standardbred horses. MD probes were introduced into the lamellar tissue under local anaesthesia. Following intravenous injection of gentamicin (5mg/kg), MD and serum samples were collected for 24h and analysed using a sensitive ELISA test for gentamicin and fluorescence polarization immunoassay for urea concentrations. Calibration of probes was performed through in vivo urea recovery and in vitro gentamicin and urea recovery. Data obtained from different body compartments were ...
Schramme AR, Pinto CR, Davis J, Whisnant CS, Whitacre MD.Current therapy protocols to treat persistent post mating endometritis and retained fetal membranes in mares typically include the administration of ecbolic drugs. Evaluation of the pharmacokinetics and tolerability of carbetocin, a long-acting oxytocin analogue, after i.v. administration is required. Objective: To determine the pharmacokinetic parameters (principally half-life) of carbetocin in horses. Methods: Five mature mares and one gelding received 0.175 mg carbetocin i.v. All animals were monitored periodically throughout the study for elevation in rectal temperature, heart rate, respir...
Sellon DC, Papich MG, Palmer L, Remund B.A two-way cross-over study of the pharmacokinetics of butorphanol after intravenous and intramuscular administration at 0.08 mg/kg in six adult horses was performed. Heparinized venous blood samples were obtained prior to drug administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV injection. Samples were obtained at the same time points and at 6 h and 12 h after IM injection. Physical examination parameters were recorded at each time point. Plasma butorphanol concentrations were determined by high performance liquid chromatography. No significant differences in any physi...
Dirikolu L, Lehner AF, Harkins JD, Woods WE, Karpiesiuk W, Gates RS, Fisher M, Tobin T.Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations p...
Rusiecki KE, Nieto JE, Puchalski SM, Snyder JR.To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses. Methods: Experimental randomized cross-over study. Methods: Healthy horses (n=6). Methods: Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produc...
De Leo M, Giorgi M, Saccomanni G, Manera C, Braca A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O-Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the micro-receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole ...
Soraci A, Jaussaud P, Benoit E, Delatour P.Fenoprofen (FPF) is a chiral non-steroid antiinflammatory drug, marketed as a racemic mixture of its R(-) and S(+) enantiomers. Its stereoselective disposition in humans and animals is due to a chiral inversion converting R(-)FPF into S(+)FPF. The first step of this reaction, which produces an acyl-CoA thioester, is catalysed by an acyl-CoA ligase. A stereospecific high performance liquid chromatography assay was used to study the disposition of FPF enantiomers in four geldings and three male beagle dogs, following intravenous doses of racemic FPF (1 mg/kg in horses), R(-)FPF (0.5 mg/kg in hor...
Sweeney RW, Sweeney CR, Soma LR, Woodward CB, Charlton CA.Serum and peritoneal fluid concentrations of metronidazole were determined in 6 healthy adult horses given the drug (25 mg/kg) by IV or oral routes. The disposition of metronidazole in horses given the drug by the IV route conformed to a 2-compartment model with a distribution half-life of 0.16 hours, an elimination half-life of 2.9 hours, and a body clearance of 0.40 +/- 0.05 L/kg/hr. The oral absorption half-life was 0.40 hours, and the bioavailability, 85.0 +/- 18.6%. Peritoneal fluid concentrations were approximately equal to serum concentrations at all times, regardless of the route of ad...
Rosa B.Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledg...
Geiser DR.Chemical restraint in the standing horse is used for a variety of procedures in veterinary medicine. The choice of agent depends on the physical status, temperament, and size of the patient; the procedure to be performed; and safety for the patient, veterinarian, and owner. The combination of certain agents may provide more desirable restraint and analgesia than does the use of individual agents. The use of analgesics in the horse is not without side effects, some of which may be detrimental to the patient's condition. Analgesics should be chosen with these untoward effects in mind. Draft bree...
Klaus AM, Schlingloff Y, Kleinitz U, Böttcher M, Hapke HJ.The pharmacokinetic behaviour of dipyrone metabolite 4-MAA in serum was determined in seven horses of different breeds after a single intravenous dose administration. A biexponential formula was fitted to the serum concentration vs. time data. The median half-life of the elimination phase (t1/2 beta) was 4.85 h (range 5.04 h), the median volume of distribution (Vd(area)) was 1.85 L/kg (range 3.2 L/kg) and median of total clearance was 4.0 mL/min/kg (range 2.3 mL/min/kg).
Lyons ET, Tolliver SC.Macrocyclic lactones (MLs) revolutionized parasite control in horses and other animals. They are unique in that they are effective against arthropods and nematodes. The first of the widely used avermectins was ivermectin. In 1983, it was marketed for use in horses as an injectable formulation but was withdrawn in 1984 after about a year and half on the market because of adverse problems. It was replaced by a paste formulation and an oral/stomach tube liquid formulation. Ivermectin is highly active on bots, ascarids, large and small strongyles, pinworms, strongyloides, stomach worms, and some o...
Wood T, Stanley S, Woods WE, Henry P, Watt D, Tobin T.This study was designed to explore the use of hematocrit values as possible indicators of the threshold doses of adrenergic drugs in the performance horse. Acepromazine, detomidine, and fluphenazine were tested for their effects on hematocrit values, with the threshold dose for these effects investigated. Hematocrit values were shown to be quite sensitive to the administration of acepromazine with doses as low as 50 micrograms/horse producing detectable depressions in hematocrit values for up to 2 hours. Increasing the dose increased the magnitude of the effect, but did not appear to prolong i...
Kwong EC, Chen FC, Young LM.The urinary excretion of a sustained-release formulation of pentoxifylline was studied in the horse after the oral administration of 4.0 grams of Trental tablets. Urine samples were collected for 24 hours after dosing and analyzed for pentoxifylline and its metabolites using high-performance liquid chromatography coupled with an ultraviolet detector. Six metabolites of pentoxifylline were identified in horse urine in addition to less than 0.2% of unchanged drug. Concomitant use of gas chromatography/mass spectrometry allowed for the elucidation of the chemical structures of the metabolites. Me...
Lyons ET, Tolliver SC, Stamper S, Drudge JH, Granstrom DE, Collins SS.Praziquantel injectable formulation was administered at 0.5 mg k-1 per os to 24 equids naturally infected with 1-183 (average 40) Anoplocephala perfoliata. Drug activity was evaluated by a modified critical test method with necropsy 24 h after treatment. There was variable efficacy of 0-100% (aggregate average 85%); for 18 equids, 93-100%, for three equids, 70-85%, and for three equids, 0-20%.
Carakostas MC, Moore WE, Smith JE, Johnson D.The functional capacity of the marrow granulocyte reserve (MGR) in 4 adult horses was studied, using 51Cr-labeled leukocytes. The mean increase in the peripheral granulocyte count following injections of etiocholanolone (0.3 mg/kg) was 870 granulocytes/mm3, and the mean increase following prednisolone administration (200 mg) was 5,880 granulocytes/mm3. Etiocholanolone failed to mobilize the MGR and decreased the rate of granulocyte egress from the blood. Prednisolone rapidly mobilized the MGR and markedly decreased the granulocyte specific activity during the first 3 hours after injection.
Hildebrand SV, Holland M, Copland VS, Daunt D, Brock N.Neuromuscular blocking agents (muscle relaxants) are useful and common adjuncts to general anesthesia for human beings, but have not been used extensively during anesthesia of large animal species. Over a 3-year period, atracurium or pancuronium were used as adjuncts to general anesthesia for 89 anesthetic procedures in 88 equids (of 18 breeds and age ranging in age from 5 weeks to 25 years) at the teaching hospital. Forty-one of the anesthetic procedures were for abdominal surgery, and orthopedic (n = 19), ophthalmologic (n = 17), thoracotomy (n = 1), and soft tissue (n = 14) procedures compo...
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.
Held F, Ekstrand C, Cvijovic M, Gabrielsson J, Jirstrand M.Cortisol is a steroid hormone relevant to immune function in horses and other species and shows a circadian rhythm. The glucocorticoid dexamethasone suppresses cortisol in horses. Pituitary pars intermedia dysfunction (PPID) is a disease in which the cortisol suppression mechanism through dexamethasone is challenged. Overnight dexamethasone suppression test (DST) protocols are used to test the functioning of this mechanism and to establish a diagnosis for PPID. However, existing DST protocols have been recognized to perform poorly in previous experimental studies, often indicating presence of ...
Segura D, Monreal L, Pérez-Pujol S, Alonso A, Díaz-Ricart M, Brugués R, Ordinas A, Escolar G.The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study, citrated blood was incubated with different concentrations of etamsylate, and P-selectin expression and annexin V binding were determined by flow cytometry. In the in vivo study, blood was collected before and 1 and 2h after IV administration of etamsylate, and P-selectin expression was evaluated. In the in vitro study, a significant increase in P-selectin exp...
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverag...
Crandall A, Hopster K, Grove A, Levine D.In horses undergoing castration, direct comparison of intratesticular lidocaine vs mepivacaine as analgesic adjuncts has not yet been analysed. Objective: To compare the effects of intratesticular lidocaine and mepivacaine during equine castration using the Henderson drill under total intravenous anesthesia. Methods: Randomised, double-blinded clinical study. Methods: Thirty-four stallions were anaesthetised using xylazine-ketamine and randomly selected to receive 10 mL either lidocaine or mepivacaine injected into each testicle. Both surgeon and anaesthetist were blinded to the selected trea...
Knych HK, Janes J, Kennedy L, McKemie DS, Arthur RM, Samol MA, Uzal FA, Scollay M.Bisphosphonates are potent anti-resorptive agents that have the potential to adversely affect bone healing in equine athletes, and normal bone adaption in young racehorses. A concern exists that bisphosphonate inhibition of normal bone metabolism could lead to increased bone fractures during high-intensity exercise. We found only a single report describing concentrations of tiludronate in the bone of horses, and no studies describing clodronate. Knowledge of the residence time in bone could allow for a better understanding of the long-term effects of these compounds. Our objectives were to dev...
Pre-clinical studies on human isolated bronchi have relevant translational value in human in vivo, conversely no investigation has been performed to assess whether data resulting from equine isolated airways can have any translational application in asthmatic horses. Thus, a meta-regression analysis via random-effect method was carried out to correlate the pharmacological characteristics of bronchodilators resulting from experiments performed in equine isolated bronchi with their impact on the lung function outcomes in asthmatic horses. Data on the potency of different bronchodilators were ext...
Soma LR, Beech J, Gerber NH.The effect of disodium cromoglycate (cromolyn) in preventing the pulmonary dysfunction caused by the inhalation of barn and hay dust was studied in 5 horses with confirmed chronic obstructive pulmonary disease (COPD). The horses were studied before (Con) and after exposure to hay and dust allergens (Expos) and after pretreatment with cromolyn followed by exposure (Cr-Expos). There was a significant reduction in PaO2 from 86.8 +/- 8.3 to 73.1 +/- 8.8 when the horses were exposed to hay and dust allergens. The PaO2 after pretreatment with cromolyn and exposures was 78.1 +/- 5.5. There were no si...
Sutton DG, Bahr A, Preston T, Cohen ND, Love S, Roussel AJ.The 13C-octanoic acid breath test has been correlated significantly to radioscintigraphy for measurement of gastric emptying indices in healthy horses. The objective of this study was to investigate the validity of the test for measurement of equine delayed gastric emptying, prior to its potential clinical application for this purpose. A model of atropine-induced gastroparesis was used. Gastric emptying rate was measured twice in 8 horses using concurrent radioscintigraphy and/or breath test after treatment i.v. with either atropine (0.035 mg/kg bwt) or saline in randomised order. Analysis of ...
Puigdemont A, Arboix M, Gaspari F, Bortolotti A, Bonati M.The protein binding of propafenone in vitro was assessed in plasma of mouse, rat, rabbit, dog, sheep, man, cow, and horse at two concentration levels. In all species and at both concentrations propafenone was found highly bound (86-99%) to plasma proteins. No significant relationship was found between free propafenone and the plasma protein fractions. A concentration-dependency was seen in plasma of mouse, sheep, man, and horse, in which the free fraction of propafenone became larger on raising the concentration. Qualitative and quantitative differences were observed in the protein plasma prof...
O'Banion MP, Sundman E, Edmonds M, Davis J.Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive da...
Friebe M, Stahl J, Kietzmann M.Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments...
Golenz MR, Wilson WD, Carlson GP, Craychee TJ, Mihalyi JE, Knox L.The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly differen...
Becher AM, Pfister K.In recent years more and more cases of anthelmintic resistant equine strongyles were reported. The latest developments are cases of resistance against macrocyclic lactones. In order to delay this process less anthelmintics and only those which have been previously tested for their efficacy on each individual farm should be used. During the grazing season 2008 faecal samples of 281 horses and 5 donkeys from 26 farms were analysed in the area of Salzburg. To 164 of these horses selective anthelmintic treatment was implemented. Every four weeks faecal samples from the 164 horses were quantitative...
Crisman MV, Wilcke JR, Correll LS, Irby MH.The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model-independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline fr...
Braim AE, Macdonald MH, Bruss ML, Stanley SD, Giri JK, Giri SN.To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Methods: 6 adult horses. Methods: A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results: Mild clinical effects...
Kim I, Cohen ND, Roussel A, Wang N.Gastric emptying studies are of great interest in human and veterinary medical research to evaluate effects of medications or diets for promoting gastrointestinal motility and to examine unintended side-effects of new or existing medications, diets, or procedures. Summarizing gastric emptying data is important to allow easier comparison between treatments or groups of subjects and comparisons of results among studies. The standard method for assessing gastric emptying is by using scintigraphy and summarizing the nonlinear emptying of the radioisotope. A popular model for fitting gastric emptyi...
