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.
Knych HK, Weiner D, McKemie DS, Traynham M, Blea J.Butorphanol is commonly administered, both by the intravenous and intramuscular routes, to racehorses to facilitate handling for diagnostic procedures. As the administration of butorphanol for therapeutic purposes is considered appropriate, in order to avoid inadvertent positive drug tests, a thorough understanding of the pharmacokinetics of this drug is necessary. In the current study, 12, exercised Thoroughbred horses were administered a single intramuscular dose of 0.1 mg/kg butorphanol, and serum and urine samples were collected at various times post drug administration for determination...
Toutain PL.Population pharmacokinetics (POP PK) is a powerful pharmacokinetic tool, which measures quantitatively, and explains the variability in drug exposure and drug effect between individuals. POP PK uses an observational (nonexperimental) approach; it is conducted in the target population living in its normal environment (e.g., farm and race-track). The strength of the POP PK approach lies in its greater relevance for the population studied in its different natural environments than experimental studies carried out in more or less biased laboratory conditions. In clinical settings, it is commonly n...
You Y, Missanelli JR, Proctor RM, Haughan J, Robinson MA.Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Sa...
Thomson ACS, McCarrel TM, Zakharov A, Gomez B, Lyubimov A, Schwark WS, Mallicote MF, Portela DA, Bisiau AL, Wakshlag JJ.The pharmacokinetics and tolerability of cannabinoids and their metabolites were determined in eight horses after enteral administration of a commercial CBD/CBDA-rich hemp oil product. Each horse was administered 2 mg/kg or 8 mg/kg CBD/CBDA or no treatment in a randomized cross-over design. Serial serum samples collected over 48 h were analyzed by high performance liquid chromatography with tandem mass spectrometry. Plasma chemistry analysis was performed at 0 h and 24 h. Vital parameters, pedometry, and blinded mentation and gait evaluations were recorded at intervals up to 24 h. ...
Reed RA, Berghaus LJ, Reynolds RM, Holmes BT, Krikorian AM, Sakai DM, Ishikawa Y, Knych HK.Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Unassigned: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at m...
Gustafsson K, Sykes BW, Verwilghen D, Palmers K, Sullivan S, van Galen G.Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are re...
Paranjape VV, Knych HK, Berghaus LJ, Cathcart J, Giancola S, Craig H, James C, Saksena S, Reed RA.Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. Unassigned: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h and 40 μg h dosing) in healthy adult horses. Unassigned: Randomised experimental study with a Latin-square design. Unassigned: Six adu...
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Toutain PL, Ohta M.Fosfomycin (FOM) is an approved veterinary medicinal product for large animals in Japan, but Clinical breakpoint (CBP) for antimicrobial susceptibility test (AST) is not defined for animals. This study aimed at conducting a pharmacokinetics/pharmacodynamics (PK/PD) analysis to determine the PK/PD cutoff for the CBP in horses. Drug concentrations following single intravenous administration (IV) of 20 mg/kg body weight (BW) FOM in nine horses were measured using liquid chromatography/mass spectrometry. The data were modelled using a nonlinear mixed-effects model, followed by Monte Carlo simulati...
Bello K, Lorch G, Papich MG, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps MA.Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. ...
Di Cesare F, Rabbogliatti V, Draghi S, Amari M, Brioschi FA, Villa R, Ravasio G, Cagnardi P.The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure. Results: In the CRI and SC groups DEX maximum concentrations (Cmax) were ...
Knych HK, Katzman S, McKemie DS, Arthur RM, Blea J.Lidocaine is a local anesthetic that is sometimes administered in combination with epinephrine. The addition of epinephrine increases the time lidocaine remains at the site of administration, thus prolonging the duration of effect. Due to their potential to prevent the visual detection of lameness, the administration of local anesthetics is strictly regulated in performance and racehorses. Recent reports of positive regulatory findings for lidocaine in racehorses suggests a better understanding of the behavior of this drug is warranted. The objective of the current study was to describe serum ...
Minamijima Y, Kuroda T, Kamiya T, Sone Y, Wakuno A, Ito H, Nomura M, Leung GN, Kinoshita K, Yamada M.This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain mo...
Estrada RJ, Alvarado GJ, Vargas A, Vargas J, Vargas D, Chacón R, Razquin P, Vindas R.To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. Methods: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. Methods: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block ...
O'Brien M, Mochel JP, Kersh K, Wang C, Troy J.Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics ...
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Yamada M, Leung GN.Vadadustat is a newly launched hypoxia-inducible factor stabilizer with anti-anemia and erythropoietic effects; however, its use in horses is expressly forbidden in both racing and equestrian competitions. Following our previous report on the pharmacokinetic study of vadadustat in horse plasma and urine, a long-term longitudinal analysis of vadadustat in horse hair after nasoesophageal administration (3 g/day for 3 days) to three thoroughbred mares is described in this study. Our main objective is to further extend the detection period of vadadustat for the purpose of doping control. Three...
Eichler F, Poźniak B, Machnik M, Schenk I, Wingender A, Baudisch N, Thevis M, Bäumer W, Lischer C, Ehrle A.Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories with interpreting CBD analytical results. Part 1: dose escalation study: Single oral administration of three escalatin...
Ortega McCormack JJ, Reed RA, Epstein KL, Camus MS, Knych HK.To determine if transdermally delivered fentanyl can achieve greater concentrations of fentanyl in synovial fluid when applied over a synovial structure. Conclusion: Application of fentanyl matrix patches directly over the CMCJ did not result in increased fentanyl concentrations in the synovial fluid of the treated intercarpal joint in normal horses.
Hobbs K, Luethy D, Davis J, Mallicote M, Torcivia C, Kulp J, Stefanovski D, Futterman C, Cooper F, van Eps A.Trazodone, a serotonin receptor antagonist and reuptake inhibitor, might be a useful adjunctive treatment in the initial management of horses with acute laminitis if it minimizes ambulation or encourages recumbency. Objective: (1) Evaluate the effects of PO trazodone on ambulatory activity and recumbency in healthy horses; and (2) assess the pharmacokinetics of multiple PO doses of trazodone. Methods: In a randomized cross-over design, 8 healthy horses received placebo or trazodone at 2 doses (2.5 and 7.5 mg/kg) PO q12h for 48 hours with a 14-day washout period between treatments. Forelimb...
Faivre C, Wong DM, Villarino NF, Court M, Gold JR.To determine the pharmacokinetics and clinical safety of acetaminophen after oral administration of 40 mg/kg q 12 hours or 60 mg/kg q 24 hours for 14 days. Methods: 12 healthy light-breed neonatal foals. Methods: 6 foals received acetaminophen at 40 mg/kg q 12 hours and 6 foals received 60 mg/kg q 24 hours for 14 days. The study dates were January 31 to April 15, 2023. Physical examinations were performed daily. Plasma disposition of acetaminophen was determined after the first, mid-point drug administration. Hematology and biochemistry analysis was performed before the study, day 7, and the l...
Vergara-Hernandez FB, Nielsen BD, Kottwitz JJ, Panek CL, Robison CI, Paris BL, Welsh TH, Bradbery AN, Leatherwood JL, Colbath AC.To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. Methods: 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. Methods: CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours ...
Bello K, Lorch G, Kim K, Toribio RE, Yan L, Xie Z, Hill K, Phelps M.Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Objective: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Methods: Six healthy Standardbred mares. Methods: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough sampl...
Knych HK, McKemie DS, Kass PH, Stanley SD, Blea J.Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood...
Gold JR, Grubb T, Court MH, Villarino NF.Acetaminophen is utilized in human infants for pain management and fever. Neonatal foals might benefit from administration of acetaminophen but effective and safe dosage regimens for neonatal foals remains to be determined. Unassigned: The objective was to determine the plasma pharmacokinetics of acetaminophen following oral administration of a single dose of 20 mg/kg or 40 mg/kg to neonatal foals. A secondary objective was to evaluate any changes in hematology and biochemistry profiles. Unassigned: Randomized study. Unassigned: Eight clinically healthy 7-9-day old Quarter Horse foals (3 c...
McLean AK, Falt T, Abdelfattah EM, Middlebrooks B, Gretler S, Spier S, Turoff D, Navas Gonzalez FJ, Knych HK.Recent approval of transdermal flunixin meglumine (FM) (Banamine®) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine t...
Atai T, Ozmaie S, Anoushepour A.This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine eye. Sixteen normal mares aged between 6 and 10 years were used for this study. Horses were randomly assigned to two groups. Eight horses in the first group received 0.2 mL of topical 1% prednisolone in one eye and the contralateral eye was used as control (0.2 mL of saline was instilled). The second group received 0.2 mL of 0.1% fluorometholone in a randomly selected eye and the contralateral eye served as control and received 0...
Di Cesare F, Negro V, Ravasio G, Villa R, Draghi S, Cagnardi P.Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood-brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatmen...
Gonzalez GA, Betbeze C, Wills R, Eddy A, Mochal-King C, Fontenot RL.To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. Methods: Randomized, masked, crossover study. Methods: Twelve healthy adult mares. Methods: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals...
Knych HK, McKemie DS, Yim S, Stanley SD, Arthur RM.Given the potential for long-term inhibition of bone remodeling/healing and detrimental effects to horses in training, bisphosphonates are tightly regulated in horseracing. Hair has proven to be an effective matrix for detection of drug administration to horses and has been particularly effective in detecting drugs for a long period of time post administration. Thus, hair may prove to be a useful matrix for detection of administration of this class of drugs. The objective of the current study was to develop an assay and assess the usefulness of hair as a matrix for long-term detection of clodr...
Mercer MA, Davis JL, McKenzie HC, Byron CR, Kelleher ME, Trager L, Cecere TE, Wilson KE, Council-Troche RM, Werre SR.Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. Objective: To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. Methods: Longitudinal. Methods: Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated ...
Science (New York, N.Y.)August 26, 1983
Volume 221, Issue 4613 823-828 doi: 10.1126/science.6308762
Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA.Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet kn...
Afable MG, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP.A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Methods: Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. Results: Response rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte glob...
Traversa D, von Samson-Himmelstjerna G, Demeler J, Milillo P, Schürmann S, Barnes H, Otranto D, Perrucci S, di Regalbono AF, Beraldo P, Boeckh A....A large survey was carried out in 2008 in Europe to evaluate the efficacy of fenbendazole (FBZ), pyrantel (PYR), ivermectin (IVM) and moxidectin (MOX), i.e. the major anthelmintic molecules used in current practice against cyathostomins affecting horses. A total of 102 yards and 1704 horses was studied in three countries: 60 yards and 988 horses from Italy, 22 and 396 from the UK, 20 and 320 from Germany. The survey consisted of Faecal Egg Count Reduction Tests (FECRTs) with a faecal egg count reduction (FECR) categorization of (I) resistance present if FECR <90% and the lower 95% confidenc...
Harder A, Schmitt-Wrede HP, Krücken J, Marinovski P, Wunderlich F, Willson J, Amliwala K, Holden-Dye L, Walker R.There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and beta-tubulin as the target of prebenzimidazoles/benz...
Hatheway CH, Snyder JD, Seals JE, Edell TA, Lewis GE.Serum levels of equine-botulism antitoxin to toxin types A, B, and E were measured in four type-A botulism patients who had received equine-botulism antitoxin. High circulating levels capable of neutralizing in excess of 1 X 10(8), 9 X 10(7), and 6 X 10(6) 50% mouse lethal doses of toxin of types A, B, and E, respectively, were detected. There was little depletion of type-A antitoxin even though two of the patients had circulating type-A toxin before treatment. The half-life for antitoxin persistence for one patient was calculated as being 6.5, 7.6, and 5.3 days for antitoxin types A, B, and E...
Iyer U, Kadambi VJ.Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic drug by means of a linker. ADCs provide a way to couple the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and, therefore, are promising new therapies for cancer. ADCs are prodrugs that are inactive in circulation but exert their cytotoxicity upon binding to the target cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic value have emphasized the important role each component plays in determining the efficacy and safety of the final ADC. Scientific adv...
Rizk MA, El-Sayed SA, Terkawi MA, Youssef MA, El Said el Sel S, Elsayed G, El-Khodery S, El-Ashker M, Elsify A, Omar M, Salama A, Yokoyama N....A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equ...
England GC, Clarke KW.In recent years the usefulness of the alpha 2 adrenoceptor agonist drugs has been recognized in equine practice. Several agents have become available and are now licensed for use in a number of countries. The principle actions of all alpha 2 adrenoceptor agonists are similar, in that they produce a reduction in heart rate and alteration of heart rhythm, an initial hypertension followed by a prolonged hypotension, a decrease in the cardiac output and respiratory depression. For clinical purposes, these agents produce sedation and analgesia, they are useful for premedication and markedly potenti...
Stellingwerff T, Decombaz J, Harris RC, Boesch C.Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation...
Laverty S, Sandy JD, Celeste C, Vachon P, Marier JF, Plaas AH.To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels. Methods: Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dos...
Block JA, Oegema TR, Sandy JD, Plaas A.Oral glucosamine (GlcN) has been widely studied for its potential therapeutic benefits in alleviating the pain and disability of osteoarthritis (OA). Its popularity has grown despite ongoing controversy regarding its effectiveness vs placebo in clinical trials, and lack of information regarding possible mechanisms of action. Here, we review the state of knowledge concerning the biology of GlcN as it relates to OA, and discuss a framework for future research directions. Methods: An editorial "narrative" review of peer-reviewed publications is organized into four topics (1) Chemistry and pharmac...
Toutain PL, Cester CC.To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and dose effects for meloxicam in horses and to propose a suitable dosage for use in clinical studies. Methods: 6 adult horses. Methods: The study was conducted by use of a randomized, Latin-square design. Arthritis was induced in the right carpal joint of each horse by administration of Freund's complete adjuvant. Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then administered. Validated endpoints including stride length and overall clinical lameness score (scale of 0 to 20) were used to assess the e...
Saxena A, Ashani Y, Raveh L, Stevenson D, Patel T, Doctor BP.To understand the role of glycosylation in the circulation of cholinesterases, we compared the mean residence time of five tissue-derived and two recombinant cholinesterases (injected intravenously in mice) with their oligosaccharide profiles. Monosaccharide composition analysis revealed differences in the total carbohydrate, galactose, and sialic acid contents. The molar ratio of sialic acid to galactose residues on tetrameric human serum butyrylcholinesterase, recombinant human butyrylcholinesterase, and recombinant mouse acetylcholinesterase was found to be approximately 1.0. For Torpedo ca...
Ryan D, McKemie DS, Kass PH, Puschner B, Knych HK.The increasing availability of cannabidiol (CBD) and anecdotal reports of its anti-inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD...
Kleinheinz J, Jung S, Wermker K, Fischer C, Joos U.Current approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model. Methods: Release kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with lig...
Collins P.In vitro sensitivity data suggest that acyclovir should be effective against clinical manifestations of herpes simplex virus types 1 and 2, varicella-zoster virus and possibly Epstein-Barr virus. The clinical potential against herpes simplex virus types 1 and 2 is further supported by results in animal models. Human cytomegalovirus and the veterinary herpes viruses, with the possible exception of equine herpes virus type 1, may be insufficiently sensitive to be amenable to treatment.
Sangster NC.Anthelmintic-resistance has emerged as a problem in several animal industries. In the horse, cyathostome resistance to all available treatments except for the avermectin/milbemycins means that these drugs provide the cornerstone of control. Ivermectin has been available for several years; the related compound moxidectin is more recent. Although we do not know for sure, aspects of moxidectin such as its persistent action and its efficacy against mucosal stages of cyathostomes, may enhance the rate of development of resistance. On the other hand, selection pressure would be reduced if the persis...
Saxena A, Raveh L, Ashani Y, Doctor BP.Cholinesterases are serine hydrolases that can potentially be used as pretreatment drugs for organophosphate toxicity, as drugs to alleviate succinylcholine-induced apnea, and as detoxification agents for environmental toxins such as heroin and cocaine. The successful application of serum-derived cholinesterases as bioscavengers stems from their relatively long residence time in the circulation. To better understand the relationship between carbohydrate structure and the stability of cholinesterases in circulation, we determined the monosaccharide composition, the distribution of various oligo...
Stock ML, Elazab ST, Hsu WH.Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.
Salama AA, Aboulaila M, Moussa AA, Nayel MA, El-Sify A, Terkawi MA, Hassan HY, Yokoyama N, Igarashi I.Fusidic acid known to has antibacterial, antifungal, and antimalarial activities. Fusidic acid blocks translation elongation factor G gene in Plasmodium falciparum. In the present study, the inhibitory effects of fusidic acid on the in vitro growth of bovine and equine Babesia parasites were evaluated. The inhibitory effect of fusidic acid on the in vivo growth of Babesia microti was also assessed. The in vitro growth of four Babesia species that were tested was significantly inhibited (P<0.05) by micromolar concentrations of fusidic acid (IC(50) values=144.8, 17.3, 33.3, and 56.25 μM for ...
Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S.To compare the pharmacokinetics of glucosamine and the synovial fluid levels attained following treatment with glucosamine sulphate or glucosamine hydrochloride in a large animal model at clinically relevant doses. Methods: Eight adult female horses were used. Crystalline glucosamine sulphate (Dona) or glucosamine hydrochloride was administered at a dose of 20 mg/kg by either intravenous (i.v.) injection or nasogastric (n.g.) intubation. Plasma samples were collected before dosing and at 5, 15, 30, 60, 120, 360, 480 and 720 min after dosing. Synovial fluid samples were collected from the radio...
Rubio-Martínez LM, Cruz AM.Regional limb perfusion involves administration of an antimicrobial solution into the vasculature of a selected portion of the limb that has been isolated from the systemic circulation by controlled application of a tourniquet. The technique provides high antimicrobial concentrations in the region of interest and greatly contributes to the elimination of infection.
Gokbulut C, McKellar QA.Internal parasites of horses comprise an intractable problem conferring disease, production and performance losses. Parasitism can rarely be controlled in grazing horses by management alone and anthelmintic drugs have formed the basis of therapy and prophylaxis for the last sixty years. The pharmacology of the anthelmintic drugs available dictate their spectrum of activity and degree of efficacy, their optimal routes of administration and characteristics which prevent some routes of administration, their safety tolerance and potential toxicities and as a consequence of their persistence in the...
Hines SA, Ramsay JD, Kappmeyer LS, Lau AO, Ojo KK, Van Voorhis WC, Knowles DP, Mealey RH.The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods: We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both imidocarb dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro imidocarb dipropionate ...
Giguère S, Sweeney RW, Bélanger M.To investigate the pharmacokinetics of enrofloxacin in adult horses. Methods: 2-dose oral and i.v. cross-over trial followed by multiple oral doses. Methods: 8 clinically normal adult horses. Methods: Enrofloxacin was administered at dosages of 2.5 mg/kg of body weight to 4 horses and 5.0 mg/kg to 4 other horses. Each dose was given by the intragastric and i.v. routes, using a cross-over design. After the first intragastric dose, 5 additional doses were administered at 12-hour intervals. Enrofloxacin concentrations were measured in serum, synovial fluid, peritoneal fluid, urine, CSF, and endom...
Lavoie JP, Léguillette R, Pasloske K, Charette L, Sawyer N, Guay D, Murphy T, Hickey GJ.To evaluate whether the leukotriene (LT) D4 receptor antagonist L-708,738 is therapeutically beneficial in treating horses with recurrent airway obstruction (heaves). Methods: 12 adult horses with heaves and healthy lung lobes from 20 slaughtered horses. Methods: Lung lobes were used for smooth muscle tension and radioligand binding studies. Horses with heaves were given a placebo for 14 days and administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h) or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from days 14 to 28. Pulmonary function was measured weekly for 36 days, and bronchoalveolar cells were...
Struff WG, Sprotte G.Mammals supply their newborn before birth, at birth or shortly after birth with antibodies, immunocytes and humoral constituents. This "borrowed immunity" is a form of passive immunization to protect the newborn against environmental pathogens until it establishes its own pathogen recognition and disposal systems. In cows, goats, horses and some other animal species, most immunoglobulins are obtained from the colostrum, the first milk after birth, via the gut but in humans the majority of immunoglobulins, and those of the IgG-class in particular, are acquired from the mother by placental trans...
