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.
Bousquet-Mélou A, Schneider M, El Garch F, Broussou DC, Ferran AA, Lallemand EA, Triboulloy C, Damborg P, Toutain PL.Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objective: To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Methods: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. M...
Schoster A, Amsler M, Kirchgaessner C, Saleh L, Schwarzwald C, Schmitt S.The optimal dosage regimen of gentamicin in horses is still under investigation. The objectives of this study were to determine gentamicin plasma concentrations in hospitalized horses treated with 10 mg/kg gentamicin (IV, q 24 h) and to determine whether a plasma concentration to minimum inhibitory concentration (MIC) ratio of 10:1 is reached for equine pathogens using this dose. Methods: Prospective clinical observational study; retrospective study on MICs of 131 gram-negative bacteria isolated from horses (2012-2015). Methods: University teaching hospital. Methods: Ninety-eight horses >...
Khusro A, Aarti C, Buendía-Rodriguez G, Arasu MV, Al-Dhabi NA, Barbabosa-Pliego A.Antibiotics-based therapy plays a paramount role in equine medicine because of their potential pharmacokinetics and pharmacodynamics properties. Conventional antibiotics show bacteriostatic and bactericidal properties by interfering bacterial cell wall and protein synthesis as well as inhibiting RNA polymerase, DNase 1, and DNA gyrase. Antibiotics are extensively used not only for the treatment of varied bacterial infections but also the prevention of postoperative and secondary infections. Surprisingly, antibiotics such as sulfonamides or trimethoprim/sulfonamide combinations, benzylpenicilli...
Hanafi AL, Reed RA, Trenholme HN, Sakai DM, Ryan CA, Barletta M, Quandt JE, Knych HK.To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Methods: prospective, randomized, blinded, crossover trial. Methods: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were c...
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...
Vyniarska A, Ziółkowski H, Madej-Śmiechowska H, Jaroszewski JJ.The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight. Blood samples were collected for 96 hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high-performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90 min after ivermectin administration and was...
Alonso JM, Martins ES, Peccinini RG, Rosa GS, Guerra ST, Ribeiro MG, Santos B, García HDM, Watanabe MJ, Takahira RK, Rodrigues CA, Alves ALG....Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25 mg/kg bwt) in additi...
Lee DH, Birhanu BT, Lee EB, Lee SJ, Boby N, Park YS, Park SC.Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefqui...
Checura CM, Momont HW, Castañeira C, Flores-Bragulat A, Losinno L.In horses, prostaglandin E (PGE) is produced by embryos around Day 5 post-ovulation; PGE functions directly at the oviduct promoting embryo transport into the uterus. Non-surgical collection of horse embryos for cryopreservation is recommended at Day 6.5-7 post-ovulation. It was proposed that misoprostol administered orally will hasten oviductal transport of horse embryos. In Experiment 1 (n = 15) there was comparison of time of embryo recovery (Day 6 and 6.5 post-ovulation) from mares administered misoprostol (Day 5 and 5.5) orally to that of untreated mares. On Day 6, embryo collections were...
Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK.Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Hors...
Kuroda T, Nagata SI, Tamura N, Kinoshita Y, Niwa H, Mita H, Minami T, Fukuda K, Hobo S, Kuwano A.To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in healthy Thoroughbreds and simulate pleural fluid concentrations following multiple dose administration every 8 hours. Methods: 4 healthy Thoroughbreds. Methods: Metronidazole and imipenem were administered, and samples of plasma and pleural fluid were collected at predetermined time points. Minimum concentrations of metronidazole and imipenem that inhibited growth of 90% of isolates (MIC90), including 22 clinical Bacteroides iso...
De Ridder T, Ruppin M, Wheeless M, Williams S, Reddell P.Tigilanol tiglate is a novel small molecule approved as a veterinary pharmaceutical in Europe for intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors. The drug has a "tumor agnostic" mode of action associated with induction of an acute inflammatory response at the treatment site, immune cell recruitment, and disruption of tumor vasculature. Consequently, tigilanol tiglate has potential in treating a range of tumor types in humans and companion animals. However, it is likely that species-specific dosing and concomitant medication protocols will be required, especia...
Sierra-Rodriguez T, Groover ES, Lascola KM, Mora-Pereira M, Lee YH, Duran SH, Ravis WR, Spangler E, Hathcock T, Wooldridge AA.Voriconazole (VRC) is a potential treatment for pneumomycosis in horses. The objectives of this study were to determine if the delivery of Vfend using a Flexineb nebulizer produced clinically significant [VRC] in lower airways. The hypothesis was that [VRC] after delivery by nebulization would be greater in the pulmonary epithelial lining fluid than plasma. A secondary objective was to determine [VRC] in upper airways through the collection of nasopharyngeal wash (NPW) samples. Voriconazole solution [Vfend-6.25 mg/mL, 100 (n = 2), 200 (n = 3), 500 (n = 1) mg] was nebulized once in 6 health...
Brütsch DR, Hunziker P, Pot S, Tappeiner C, Voelter K.Intraocular fibrin clots caused by severe uveitis can be a sight-threatening condition that needs to be resolved quickly and reliably. Intracameral injection of tissue-plasminogen activator (tPA) is commonly used to resolve intraocular fibrin. However, the drug does not reach fibrinolytic concentrations after topical application. Desmoteplase (DSPA) is a structurally similar but smaller fibrinolytic agent with a higher fibrin selectivity, a longer half-life, and better biocompatibility compared with tPA. This study was designed to evaluate the corneal and scleral permeability of DSPA in rabbit...
Weber LA, Puff C, Kalbitz J, Kietzmann M, Feige K, Bosse K, Rohn K, Cavalleri JV.The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-d...
Machin J, Childers T, Kudrimoti S, Eisenberg R, Fenger C, Hartmann P, Maylin G, Shults T, Tobin T.Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemical source by being metabolized in the plant or the horse to aminorex. In Brassicaceae, glucobarbarin is hydrolyzed by myrosinase to yield barbarin, which serves as an insect repellant and/or attractant and is structurally related to aminorex. The synthesis, purification...
Shihadih DS, Harris TR, Kodani SD, Hwang SH, Lee KSS, Mavangira V, Hamamoto B, Guedes A, Hammock BD, Morisseau C.The veterinary pharmacopeia available to treat pain and inflammation is limited in number, target of action and efficacy. Inhibitors of soluble epoxide hydrolase (sEH) are a new class of anti-inflammatory, pro-resolving and analgesic drugs being tested in humans that have demonstrated efficacy in laboratory animals. They block the hydrolysis, and thus, increase endogenous concentrations of analgesic and anti-inflammatory signaling molecules called epoxy-fatty acids. Here, we screened a library of 2,300 inhibitors of the sEH human against partially purified feline, canine and equine hepatic sEH...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Sutton GA, Kelmer G. The aim of this study was to determine the time (T) to the maximum concentration (C) of amikacin sulphate in synovial fluid of the radiocarpal joint (RCJ) following cephalic intravenous regional limb perfusion (IVRLP) using 2 g of amikacin sulphate. Methods: Cephalic IVRLP was performed with 2 g of amikacin sulphate diluted in 0.9% NaCl to a total volume of 100 mL in six healthy adult mixed breed mares. An Esmarch's rubber tourniquet was applied for 30 minutes and the antibiotic solution was infused through a 23-gauge butterfly catheter. Synovial fluid was collected from the RCJ ...
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...
Bermingham E, Davis JL, Whittem T.The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than th...
Hamamoto-Hardman BD, Baden RW, McKemie DS, Knych HK.Uridine diphospho-glucuronosyltransferases (UGTs) are membrane-bound enzymes that catalyze the conjugation of glucuronic acid onto a diverse set of xenobiotics. Horses efficiently and extensively glucuronidate a number of xenobiotics, including opioids, making UGTs an important group of drug-metabolizing enzymes for the clearance of drugs. Recombinant enzymes have allowed researchers to characterize the metabolism of a variety of drugs. The primary objective was to clone, express and characterize equine UGTs using drugs characterized as UGT substrates in other species. A secondary objective wa...
Ocampo L, Coello M, Aquino I.The aim of this study was to compare the effects of cisapride and tegaserod on intestinal smooth muscle activity in equines. Efficacy was evaluated through measurement of gastrointestinal transit time, bowel movements per day, stool weight, and bowel sounds. Drug safety was evaluated via heart rate, respiratory rate, and rectal temperature. Records were obtained throughout three periods: a control phase without treatment, a period of cisapride administration at a dose of 0.22 mg/kg, and a period of tegaserod treatment at a dose of 0.27 mg/kg. Gastrointestinal transit time, bowel movements pe...
Le KM, Caston SS, Hossetter JM, Hay Kraus BL.To evaluate the analgesic and tissue effects of liposomal bupivacaine administered SC as an abaxial sesamoid nerve block in horses with experimentally induced lameness. Methods: 6 healthy mature light-breed horses. Methods: In a randomized crossover study, a circumferential hoof clamp was applied to a forelimb to induce reversible lameness. An abaxial sesamoid nerve block of the lame forelimb was performed by SC perineural injection of 10 mg of liposomal bupivacaine or bupivacaine HCl/site. Quantitative gait data were objectively obtained with a body-mounted inertial sensor system before (base...
Ferreira da Cruz FS, Natalini CC, Pellin de Molnar BF, Beatriz da Silva Serpa P, Tisotti T, Midon M, Desessards de La Côrte F.This study aimed to evaluate the effects and lameness degree in horses administered tramadol after the P-glycoprotein (P-gp) enteric inhibitor ivermectin. Six horses were randomly distributed into three groups, which received two different doses of tramadol by a nasogastric tube: 1 mg/kg (tramadol group 1(GT1)), 4 mg/kg (tramadol group 4 (GT4)), and tramadol 1 mg/kg combined with ivermectin 0.2 mg/kg PO (ivermectin tramadol group (GT1 + Ive)), with one-week washout interval. Heart rate (HR), respiratory rate (RR), intestinal motility, body temperature, and the degree of lameness were eval...
Knych HK, Weiner D, Arthur RM, Baden R, McKemie DS, Kass PH.Corticosteroids are potent anti-inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations. Blood and urine samples were collected prior to and for up to...
Schumacher SA, Toribio RE, Scansen B, Lakritz J, Bertone AL.The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO ) to healthy horses. MgSO is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitor...
Ortillés Á, Sanmartí J, Ríos J, Armengou L, Peña MT, Leiva M.To evaluate the effect of topical cyclopentolate hydrochloride (CH) on quantitative pupillometric readings (PR), tear production (TP), and intraocular pressure (IOP) in healthy horses. Methods: Fourteen client-owned horses. Methods: In a two-phase design study, each animal received 1% CH ophthalmic solution in the left eye [treated] and 0.9% NaCl in the right eye [control] (0.2 mL each). In the first phase (n = 7), TP, IOP, and PR assessment was performed by Schirmer tear test I, rebound tonometry and static pupillometry, at 1, 8, 24, 48, 72, 96, 120, 148, 172, and 196-hours post-instillati...
Kaps M, Okada CTC, Gautier C, Aurich J, Scarlet D, Kuhl J, Aurich C.Behavior during the estrous cycle of mares can affect their performance and therefore inhibition of cyclical ovarian activity is indicated. We hypothesized that implants containing the GnRH analog deslorelin downregulate GnRH receptors and inhibit ovulation in mares. The estrous cycles of Shetland mares were synchronized with 2 injections of a PGF analog. One day after the second injection (day 0), mares received 9.4 (group D1, n = 6) and 4.7 mg deslorelin (D2, n = 5) as slow-release implants or 1.25 mg short-acting deslorelin as a control (C, n = 5). Ultrasonography of the reproductive trac...
Burton AJ, Giguère S, Arnold RD.Although gentamicin is highly active against Rhodococcus equi in vitro, its clinical efficacy has been limited presumably due to poor cellular uptake. Encapsulation of drugs in liposomes enhances their cellular uptake. Objective: To compare the disposition of liposomal gentamicin (LG) and free gentamicin (FG) in the plasma, pulmonary epithelial lining fluid and bronchoalveolar cells of healthy foals after i.v. administration or by nebulisation, and to assess the tolerability of the drug after repeated i.v. dosing. Methods: Experimental study. Methods: Eight healthy foals received a single i.v....
Kellon EM, Gustafson KM.Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia...
Kramer CM, Tsang AS, Koenig T, Jeffcott LB, Dart CM, Dart AJ.To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. Methods: Practitioners were contacted by email, which contained a link to an online survey. Results: A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80....
Fultz L, Giguère S, Berghaus LJ, Grover GS, Merritt DA.Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data. Objective: To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation. Methods: Randomised experimental study. Methods: Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. ...
The goal of the current study was to evaluate the comparative efficacy of ivermectin (IVM) against small strongyles (cyathostomins) following its oral and intramuscular (IM) administration, in naturally parasitized horses. The parasitological data were complemented with the assessment of the plasma disposition kinetics of IVM. The trial included two different experiments. In experiment I, 40 horses naturally infected with small strongyles were randomly allocated into four experimental groups (n=10) and treated with IVM (0.2mg/kg) as follows: IVM oral paste, animals were orally treated with Eqv...
Landoni MF, Lees P.Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three-period cross-over study using a tissue cage model of inflammation. For both S(+)-and R(-)-KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degre...
DiPietro JA, Hutchens DE, Lock TF, Walker K, Paul AJ, Shipley C, Rulli D.A clinical trial carried out over 98 days was done to evaluate treatment of horses with moxidectin gel for efficacy as measured by (1) reduction in the production of parasite ova post treatment, (2) a comparison of the posttreatment parasite egg count suppression of moxidectin to ivermectin, and (3) assessment of the field safety, animal acceptance of the moxidectin formulation, and the utility of the moxidectin delivery device. One hundred and fifty Standardbred horses with naturally acquired parasite infections were used in the study. Moxidectin had more prolonged and greater suppressive inf...
Paccamonti DL, Pycock JF, Taverne MA, Bevers M, Van Der Weijden GC, Gutjahr S, Schams D, Blouin D.We investigated the half-life of oxytocin in reproductively normal mares and the prostaglandin response after oxytocin administrations. Mares were given oxytocin, 10 or 25 iu, i.v., on the day of, or 2 days after, ovulation, and frequent jugular blood samples were collected for analysis of oxytocin and Prostaglandin F metabolite (PGFM) by RIA. Neither dose of oxytocin nor day of treatment affected the half-life of the exogenous oxytocin, which was determined to be 6.8 min. A significant increase in PGFM was observed within 6 min of oxytocin administration and peak values were observed within 1...
Sjostrom L, al-Abdulla IH, Rawat S, Smith DC, Landon J.Commercial antivenoms produced in horses were compared with monospecific antivenoms raised in sheep against Crotalus durissus terrificus, Crotalus atrox, Crotalus adamanteus, Micrurus fulvius fulvius, Naja naja, Naja kaouthia, Echis ocellatus, Vipera lebetina deserti, Vipera berus berus and Vipera ammodytes ammodytes venom. Antibodies raised by immunizing sheep with C. d. terrificus venom were more effective than their equine counterparts in preventing lethal toxicity in mice (ED50), in inhibiting the venom's pharmacological effects (haemolysis, platelet aggregation and coagulation), and in ne...
Bryant JE, Brown MP, Gronwall RR, Merritt KA.The objectives of this study were to determine the pharmacokinetics and tissue concentrations of doxycycline after repeated intragastric administration, and to determine the minimum inhibitory concentrations (MIC) for equine pathogenic bacteria. In experiment 1, 2 mares received a single intragastric dose of doxycycline hyclate (3 mg/kg bwt). Mean peak serum concentration was 0.22 microg/ml 1 h postadministration. In experiment 2, 5 doses of doxycycline hyclate (10 mg/kg bwt), dissolved in water, were administered to each of 6 mares via nasogastric tube at 12 h intervals. The mean +/- s.e. pea...
Cox S, Villarino N, Sommardahl C, Kvaternick V, Zarabadipour C, Siger L, Yarbrough J, Amicucci A, Reed K, Breeding D, Doherty T.The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the L...
Guptill JT, Raja SM, Juel VC, Walter EB, Cohen-Wolkowiez M, Hill H, Sendra E, Hauser B, Jackson P, Swamy GK.Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments, including an equine antitoxin and human immune globulin, are given postexposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy vol...
Lankveld DP, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE, van Dijk P, Hellebrekers LJ.Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, non...
YAMASHITA K, AKASHI N, KATAYAMA Y, UCHIDA Y, UMAR MA, ITAMI T, INOUE H, SAMS RA, MUIR WW.The bispectral index (BIS) was evaluated as an indicator of central nervous system (CNS) depression in horses anesthetized with propofol. Five non-premedicated horses were anesthetized with 7 mg/kg, IV propofol and the minimum infusion rate (MIR) of propofol required to maintain anesthesia was determined during intermittent positive pressure ventilation in each horse. The BIS was determined 20 min later and after stabilization at 2.0 MIR, 1.5 MIR, and 1.0 MIR. The BIS was also recorded after the cessation of propofol infusion when the horses regained spontaneous breathing and swallowing reflex...
Bentz BG, Maxwell LK, Erkert RS, Royer CM, Davis MS, MacAllister CG, Clarke CR.The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between eac...
Gardner SY, Papich MG.The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs. Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs. Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse-phase high-performance liquid chromatography (HPLC). Cefepime concentrations in both groups of animals were described by a two-compartment pharmacokinetic model with elimination half-lives of 1.65 and 1.09 h for the foal ...
Jacks S, Giguère S, Gronwall PR, Brown MP, Merritt KA.To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. Methods: 6 healthy 6- to 10-week-old foals. Methods: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Resul...
Figueiredo JP, Muir WW, Sams R.To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain. Methods: 6 healthy adult horses. Methods: Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variabl...
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...
Marroum PJ, Webb AI, Aeschbacher G, Curry SH.A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pat...
Hopster K, Müller C, Hopster-Iversen C, Stahl J, Rohn K, Kästner S.To compare cardiovascular effects and recovery quality and duration of total intravenous anaesthesia (TIVA) with xylazine-ketamine-midazolam or dexmedetomidine-ketamine-midazolam. Methods: Prospective, randomized experimental cross-over trial. Methods: Eight adult warmblood horses. Methods: After sedation with acepromazine and either xylazine [0.5 mg kg(-1) , intravenously (IV)] or dexmedetomidine (3.5 μg kg(-1) IV) anaesthesia was induced with ketamine and midazolam and maintained with a constant rate infusion (CRI) of xylazine (1 mg kg(-1) hour(-1) ) [XKM] or dexmedetomidine (7 μg...
Latimer FG, Colitz CM, Campbell NB, Papich MG.To determine the pharmacokinetics of fluconazole in horses. Methods: 6 clinically normal adult horses. Methods: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined i...
Delekta PC, Dobry CJ, Sindac JA, Barraza SJ, Blakely PK, Xiang J, Kirchhoff PD, Keep RF, Irani DN, Larsen SD, Miller DJ.Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solub...
Spelta CW.Equine pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disease of the hypothalamus, resulting in the loss of dopaminergic inhibition of pars intermedia. An oxidative stress injury of unknown etiology has been suggested to initiate the neurodegeneration. While hypertrichosis (formerly known as hirsutism) is considered pathognomic for advanced disease, the antemortem diagnosis of subclinical and early disease has continued to prove difficult. Numerous tests have been used with varying sensitivities and specificities. The overnight dexamethasone suppression test, originally do...
Frank M, Weckman TJ, Wood T, Woods WE, Tai CL, Chang SL, Ewing A, Blake JW, Tobin T.Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sw...
Gokbulut C, Cirak VY, Senlik B, Aksit D, Durmaz M, McKellar QA.Pour-on formulations of endectocides decrease the risk of injury for both user and animal, and are particularly convenient for animal owners who can apply the product. This study was designed to investigate the plasma disposition and efficacy of ivermectin (IVM) following pour-on, per os and intravenous administrations. Eighteen female horses weighing 510-610 kg were used in this study. The animals were allocated into three groups (per os, pour-on and intravenous groups). The equine paste, bovine pour-on and bovine injectable formulations of IVM were administered orally, topically and intraven...
Barton MH, Paske E, Norton N, King D, Giguère S, Budsberg S.Two firocoxib preparations for oral use are approved for use in animals in many countries: a chewable canine tablet and an equine paste. In order to reduce costs, many veterinarians use the canine product in horses even though this is an off-label use of the preparation. Objective: To determine the relative efficacy of 2 commercially available firocoxib products to inhibit prostaglandin E₂ (PGE2) synthesis after oral dosing in horses. Methods: A crossover design using 8 adult horses (n = 4 for each preparation during each treatment period). Body weight range 532-614 kg. Methods: Horses recei...
Ducharme NG, Fubini SL.Atropine sulfate was given at 2 dosages (0.044 mg/kg, 0.176 mg/kg) to clinically normal ponies in order to evaluate the drug's effect on the gastrointestinal tract. Intestinal motility, as assessed by ausculation of borborygmus, was stopped 30 minutes after injection, but it gradually returned to normal within 12 hours. Signs of abdominal pain developed in 3 of 10 ponies. In 3 clinical cases of gastrointestinal disorder, prior atropine treatment was confusing to the diagnostician and resulted in delayed surgical treatment in 1 case. It was concluded that atropine should not be used for allevia...
Dahan R, Oreff GL, Tatz AJ, Raz T, Britzi M, Kelmer G.The objectives of this study were to evaluate the compatibility and the pharmacokinetic properties of combined amikacin and penicillin administration by intravenous regional limb perfusion (IVRLP) in horses. A tourniquet was applied proximal to the carpus of 7 clinically healthy adult horses and 2 g of amikacin and 10 × 10 IU of penicillin (100 mL total volume) were sequentially injected into the cephalic vein just distal to the tourniquet. Synovial samples were collected from the joint at several times after injection. All samples were analyzed for amikacin and penicillin concentration. The ...
