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.
Davis JL, Salmon JH, Papich MG.To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses. Methods: 6 adult horses. Methods: The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions. Results: Feeding ...
Feary DJ, Mama KR, Thomasy SM, Wagner AE, Enns RM.To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease. Methods: 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40 kg). Methods: Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentration...
Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC.To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. Methods: 11 healthy adult horses. Methods: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via...
Natalini CC, Linardi RL.To evaluate the effects of epidural administration of hydromorphone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Methods: 6 healthy adult horses. Methods: Horses were assigned to receive hydromorphone (0.04 mg/kg) or a control solution (20 mL of sterile water) administered epidurally into in the first intercoccygeal space. Treatments were administered at time intervals of > or = 7 days. Electrical stimulation was applied for 6 hours after epidural injection over the dermatomes of the perineal, sacral, lumbar, and t...
Bosch G, van Duijkeren E, Bergwerff AA, Rijkenhuizen AB, Ensink JM.Ceftiofur concentrations in an infected and uninfected environment were compared and the efficacy of locally administered ceftiofur was evaluated in an experimental infection with Staphylococcus aureus in tissue cages. Eight ponies had tissue cages (TCs) implanted s.c. on each side of the neck. Into one of the cages 150 mg of ceftiofur was administered and fluid samples were taken to determine ceftiofur concentrations. After 1 week the other TC was infected with S. aureus and subsequently treated with 150 mg ceftiofur administered locally into the TC once daily for 21 days. Samples of fluid we...
Zerpa H, Bailey SR, Berhane Y, Elliott J.Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been implicated in a number of conditions, such as acute equine laminitis, and are therapeutic targets for the treatment of this condition. Digital veins, rather than arteries, were investigated in the present study because they have been specifically implicated in the pathophysiology of acute laminitis. The order of potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists was determined in isolated rings of EDVs under ...
Mills PC, Cross SE.Little is known about the transdermal penetration of hydrocortisone in the horse and, although commercial formulations containing hydrocortisone are registered for topical use in the horse, there have been no studies investigating the movement of this glucocorticoid through different regions of equine skin. Skin was harvested from the thorax, groin and leg (dorsal metacarpal) regions of five Thoroughbred geldings and frozen (-20 degrees C) until required. Defrosted skin was placed in Franz-type diffusion cells and the amount of radiolabelled ((3)H) hydrocortisone, in a saturated solution of un...
Myrna KE, Herring IP.To assess the efficacy and kinetics of a continuous infusion modality for topical ophthalmic drug delivery via subpalpebral lavage in horses. Methods: Five ophthalmically normal horses Methods: A constant-rate continuous delivery pump was used to apply 0.01% fluorescein solution to the eyes of five ophthalmically normal horses via subpalpebral lavage. Fluorescein was applied at a rate of 0.14 mL/h for 72 h. Tear samples were collected from the ventral conjunctival fornix at regular intervals via capillary tube and tear fluorescein concentrations were determined via spectral assay. Laboratory s...
Malone E, Ensink J, Turner T, Wilson J, Andrews F, Keegan K, Lumsden J.To determine if intravenous lidocaine is useful and safe as a treatment for equine ileus. Methods: Prospective double-blinded placebo-controlled trial. Methods: Horses (n = 32) with a diagnosis of postoperative ileus (POI) or enteritis and that had refluxed >20 L or had been refluxing for >24 hours. Methods: Refluxing horses were administered lidocaine (1.3 mg/kg intravenously [IV] as a bolus followed by a 0.05 mg/kg/min infusion) or saline (0.9% NaCl) solution placebo for 24 hours. Variables evaluated included volume and duration of reflux, time to 1st fecal passage, signs of pain, anal...
Rubio-Martínez LM, López-Sanromán J, Cruz AM, Santos M, Andrés MS, Román FS.To evaluate clinical variables, regional concentrations, and pharmacokinetics of vancomycin in the synovial fluid of distal forelimb joints of horses after IV regional limb perfusion. Methods: 6 horses. Methods: Vancomycin was administered via IV regional limb perfusion to the distal portion of the forelimbs of anesthetized horses. Drug (300 mg of vancomycin hydrochloride in 60 mL of saline [0.9% NaCl] solution) was infused into 1 forelimb, whereas the contralateral limb served as a control and was perfused with 60 mL of saline solution. Solutions were injected into the lateral digital vein af...
Scotty NC, Evans TJ, Giuliano E, Johnson PJ, Rottinghaus GE, Fothergill AW, Cutler TJ.Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 da...
Pille F, De Baere S, Ceelen L, Dewulf J, Croubels S, Gasthuys F, De Backer P, Martens A.To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. Methods: Experimental cross-over study. Methods: Five normal adult horses. Methods: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or...
Rubio-Martínez L, López-Sanromán J, Cruz AM, Santos M, San Román F.To study the pharmacokinetics of vancomycin in plasma obtained from the medullary sinusoids of the proximal phalanx (P1) after intravenous (IV) and intraosseous (IO) regional limb perfusion (RLP). Methods: Experimental study. Methods: Twelve horses. Methods: IV and IO RLP were performed in 2 groups (n = 6) of horses. Vancomycin hydrochloride (300 mg in 60 mL 0.9% NaCl) was randomly infused in 1 front limb, with the contralateral limb as control (60 mL 0.9% NaCl). A hole was drilled in the lateral cortex of P1, and blood samples from the medullary sinusoids of P1 were collected before infusion,...
Valverde A, Gunkelt C, Doherty TJ, Giguère S, Pollak AS.Lidocaine constant rate infusions (CRIs) are common as an intraoperative adjunct to general anaesthesia, but their influence on quality of recovery has not been thoroughly determined. Objective: To determine the effects of an intraoperative i.v. CRI of lidocaine on the quality of recovery from isoflurane or sevoflurane anaesthesia in horses undergoing various surgical procedures, using a modified recovery score system. Objective: The administration of intraoperative lidocaine CRI decreases the quality of recovery in horses. Methods: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min...
Guan F, Uboh CE, Soma LR, Luo Y, Rudy J, Tobin T.Anabolic androgenic steroids are related to the male sex hormones and are abused in equine sports. In an effort to deter the abuse of anabolic steroids, a sensitive LC-MS/MS method was developed for detection, quantification and confirmation of eight major anabolic steroids (testosterone, normethandrolone, nandrolone, boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, and stanozolol) in equine plasma. Formation of solvent adduct ions of the analytes was observed under electrospray ionization (ESI) conditions, and desolvation of the solvent adduct ions by source collision-in...
Davis JL, Salmon JH, Papich MG.To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. Methods: 6 healthy horses. Methods: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconaz...
Sasaki N, Aiuchi H, Yamada H.This study aimed to establish and standardize a breath test that uses 13C-acetate in a liquid diet for evaluation of gastric emptying in horses. Seven adult healthy thoroughbreds were used in this study. They were given 13C-acetate (125 mg, 250 mg, or 500 mg) in a test meal (2000 ml liquid diet) via an intranasal catheter. 13C concentrations in the exhaled CO2 were measured in samples taken before and after test meal administration using an infrared absorption spectroscope. In the 500 mg 13C-acetate group, Delta13CO2 showed a steep gradient immediately after meal administration compared to the...
White SD, Maxwell LK, Szabo NJ, Hawkins JL, Kollias-Baker C.To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of i.v. and oral administration of AZA in horses. Methods: 6 horses. Methods: In study phase 1, a single dose of AZA was administered i.v. (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for ...
Mills PC, Cross SE.Commercial formulations of non-steroidal anti-inflammatory drugs (NSAIDs) are developed for human use but the extent to which they will pass through equine skin is unknown. Skin was harvested from five Thoroughbred geldings from the thorax, groin and leg (dorsal metacarpal) regions and frozen (-20 degrees C) until required. Two grams of methylsalicylate (MeSa) gel was applied to defrosted full-thickness samples in diffusion cells and the penetration of MeSa and its active metabolite, salicylate (Sa), through skin samples were measured over 24 h. Significantly higher (P < or = 0.02) total sa...
Schwarzwald CC, Bonagura JD, Luis-Fuentes V.Quinidine is effective for treatment of atrial fibrillation (AF) in horses, but often accelerates ventricular response rate. Diltiazem effectively controls heart rate response to AF in other species. This investigation determined the effects of diltiazem on cardiac rate and rhythm, left ventricular (LV) function, central hemodynamics, and peripheral blood flow in normal, standing, nonsedated horses. A dose-finding study was performed. Afterward, 8 healthy horses were treated with diltiazem IV every 30 minutes to achieve cumulative dosages of 0 (saline control), 1, 1.5, and 2 mg/kg. Plasma dilt...
Delesalle C, Deprez P, Schuurkes JA, Lefebvre RA.The use of human prokinetic drugs in colic horses leads to inconsistent results. This might be related to differences in gastrointestinal receptor populations. The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the equine mid-jejunum were therefore studied. Longitudinal muscle preparations were set up for isotonic measurement. 5-HT induced tonic contractions with superimposed phasic activity; these responses were not influenced by tetrodotoxin and atropine, suggesting a non-neurogenic, non-cholinergic pathway. The 5-HT receptor antagonists GR 127935 (5-HT(1B,D)), ketanserin (5-HT(2A...
Kaneps AJ, Craig AM, Walker KC, True JE.To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine. Methods: 6 adult mares. Methods: Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELIS...
Davis JL, Salmon JH, Papich MG.The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume o...
Adams AR, Haines GR, Brown MP, Gronwall R, Merritt K.Pharmacokinetics of difloxacin and its distribution within the body fluids and endometrium of 6 mares were studied after intragastric (IG) administration of 5 individual doses. Difloxacin concentrations were serially measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal fluid, and endometrium over 120 h. Bacterial susceptibility to difloxacin was determined for 174 equine pathogens over a 7-month period. Maximum serum concentration (Cmax) was 2.25 +/- 0.70 microg/mL at 3.12 +/- 2.63 h and Cmax after the 5th dose was 2.41 +/- 0.86 microg/mL at 97.86 +/- 1.45 h. The mean elim...
Gilmour MA, Clarke CR, Macallister CG, Dedeo JM, Caudell DL, Morton RJ, Pugh M.To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. Results: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline oc...
Sasaki N, Okamura K, Yamada H.To examine the effects of various doses of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on motility of the small intestine and cecum in horses by use of electrical activity and to determine the dose that provides the optimal response. Methods: 6 healthy adult Thoroughbreds. Methods: Electrical activity of the small intestine and cecum was recorded before and after mosapride administration by use of an electrogastrograph. Mosapride (0.5, 1, 1.5, and 2 mg/kg) was dissolved in 200 mL of water and administered orally to horses through a nasogastric tube. Three hours after drug administrati...
Theurillat R, Knobloch M, Levionnois O, Larenza P, Mevissen M, Thormann W.A robust CE method for the simultaneous determination of the enantiomers of ketamine and norketamine in equine plasma is described. It is based upon liquid-liquid extraction of ketamine and norketamine at alkaline pH from 1 mL plasma followed by analysis of the reconstituted extract by CE in the presence of a pH 2.5 Tris-phosphate buffer containing 10 mg/mL highly sulfated beta-CD as chiral selector. Enantiomer plasma levels between 0.04 and 2.5 microg/mL are shown to provide linear calibration graphs. Intraday and interday precisions evaluated from peak area ratios (n = 5) at the lowest calib...
Dumasia MC.The in vivo biotransformation of metoprolol tartrate in the thoroughbred racehorse was studied after administration of a single oral dose. Metoprolol and its basic and bifunctional phase I metabolites were isolated from urine and plasma using mixed mode solid phase extraction (SPE) cartridges. The isolates were derivatised as trimethylsilyl ethers and analysed by capillary column gas chromatography--positive ion electron ionisation and ammonia chemical ionisation mass spectrometry. Metabolism was primarily confined to the oxidative transformations of the p-(2-methoxy)ethyl substituent. Metopro...
Lees P, Taylor JB, Higgins AJ, Sharma SC.The clinically recommended dose rate of phenylbutazone (4.4 mg/kg) was administered intravenously as a single dose to five Welsh Mountain ponies. Distribution of phenylbutazone and its active metabolite oxyphenbutazone into body fluids was studied by measuring concentrations in plasma, tissue-cage fluid, peritoneal fluid and acute inflammatory exudate harvested from a polyester sponge model of inflammation. The ready penetration of phenylbutazone into inflammatory exudate was demonstrated by the relatively high mean value for Cmax of 12.4 micrograms/ml occurring at a time of 4.6 h and a mean A...
Abu-Basha EA, Bani Ismail Z, Ababneh MM, Hamzeh E, Gehring R.This study was designed to investigate the safety and pharmacokinetic (PK) profile of tildipirosin in horses after intravenous (i.v.) and subcutaneous (s.c.) injection of a single dose at 4 mg/kg of body weight (b.w.). A total of 12 healthy mixed breed horses were used in the study. Horses were monitored for systemic and local adverse effects, and whole blood samples were collected for hematology and plasma biochemistry analysis at time (0) and at 6, 24, and 72 h after drug administration. For PK analysis, blood samples were collected at pre-determined times before and after tildipirosin adm...
Olsén L, Ingvast-Larsson C, Bondesson U, Broström H, Tjälve H, Larsson P.The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h be...
Fifteen horses harboring naturally acquired, patent Parascaris equorum and Oxyuris equi infections were equally allotted to 3 treatment groups given (1) injectable vehicle; (2) injectable ivermectin at the dose rate of 200 microgram/kg of body weight; and (3) injectable ivermectin at the rate of 300 microgram/kg. All treatments were given IM in the neck. All animals were killed 14 days after treatment and examined for the targeted nematodes. Regardless of dose rate, ivermectin proved 100% effective in the removal of adult O equi and P equorum infections. Levels of immature P equorum were decre...
Bettschart-Wolfensberger R, Taylor PM, Sear JW, Bloomfield MR, Rentsch K, Dawling S.To examine the physiologic and pharmacokinetic effects of a technique of total intravenous anesthesia in ponies. Methods: 6 healthy ponies. Methods: Ponies were premedicated with acepromazine (0.03 mg/kg of body weight, IV) and xylazine (1.0 mg/kg, IV). Two minutes later, anesthesia was induced with ketamine (2.0 mg/kg, IV) followed by climazolam (0.2 mg/kg, IV). Anesthesia was maintained for 120 minutes by an infusion of climazolam (0.4 mg/kg/h) and ketamine (6.0 mg/kg/h). Oxygen (5 L/min) was supplemented. 20 minutes after the infusion was stopped sarmazenil (0.04 mg/kg, IV) was administered...
Rezende ML, Boscan P, Stanley SD, Mama KR, Steffey EP.To characterize cardiovascular, respiratory and biochemical effects and recovery behavior associated with a 3-hour continuous infusion of a micellar microemulsion propofol formulation in horses. Methods: Prospective experimental trial. Methods: Six healthy adult horses, 9 +/- 2 years old and weighing 557 +/- 14 kg. Methods: All horses received xylazine (1 mg kg(-1), IV) 5 minutes prior to anesthetic induction. Each horse was anesthetized on two occasions with a 5% micellar microemulsion propofol formulation (2 mg kg(-1), IV); first as a single bolus (phase I) and then as a 3-hour continuous in...
Baker SJ, Gerring EL.We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administr...
Gozalo-Marcilla M, Moreira da Silva R, Pacca Loureiro Luna S, Rodrigues de Oliveira A, Werneck Fonseca M, Peporine Lopes N, Taylor PM, Pelligand L.The alpha(α) -agonist detomidine is used for equine sedation with opioids such as methadone. We retrieved the data from two randomized, crossover studies where detomidine and methadone were given intravenously alone or combined as boli (STUDY 1) (Gozalo-Marcilla et al., 2017, Veterinary Anaesthesia and Analgesia, 2017, 44, 1116) or as 2-hr constant rate infusions (STUDY 2) (Gozalo-Marcilla et al., 2019, Equine Veterinary Journal, 51, 530). Plasma drug concentrations were measured with a validated tandem Mass Spectrometry assay. We used nonlinear mixed effect modelling and took pharmacokinetic...
Karakka Kal AK, Nalakath J, Kunhamu Karatt T, Perwad Z, Mathew B, Subhahar M.The detection and separation of medetomidine enantiomers from the complex biological matrices poses a great analytical challenge, especially in the field of forensic toxicology and pharmacology. Couple of researchers reported resolution of medetomidine using protein-based chiral columns, but the reported method is quiet challenging and tedious to be employed for routine analysis. This research paper reported a method that enables the enantio-separation of medetomidine by using polysaccharide cellulose chiral column. The use of chiralcel OJ-3R column was found to have the highest potential for ...
Roussel AJ, Hooper RN, Cohen ND, Bye AD, Hicks RJ, Bohl TW.To evaluate the effect of erythromycin on motility of the ileum, cecum, and pelvic flexure of horses during the postoperative and post-recovery periods. Methods: 8 healthy adult horses. Methods: Horses were anesthetized and bipolar electrodes were implanted in smooth muscle of the ileum, cecum, and pelvic flexure. Approximately 4, 16, and 24 hours (postoperative recording sessions) and at least 8 days (post-recovery recording session) after surgery, myoelectric activity was recorded before and after administration of erythromycin (0.5 mg/kg). Results: Following erythromycin administration, myo...
Kimura S, McCoy AM, Boothe DM, Wooldridge AA, Graff E, Hammack SM, Cresci L, Hofmeister E, Lascola KM.To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses. Methods: 6 healthy geldings. Methods: A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentrat...
Guan F, Uboh CE, Soma LR, Birks EK, Teleis D, Rudy JA, Watson AO, Tsang DS.A reliable and sensitive method for the extraction and quantification of phenytoin (5,5'-diphenylhydantoin), its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) in horse urine and plasma is described. The method involves the use of solid-phase extraction (SPE), liquid-liquid extraction (LLE), enzyme hydrolysis (EH) and high-performance liquid chromatography (HPLC). The minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) was not present in a reliably quantifiable concentration in all samples. The ...
Landoni MF, Lees P.The bioavailability of S(+) and R(-) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil-based paste containing micronised rac-KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil-based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intraveno...
Nakayama SM, Ikenaka Y, Hayami A, Mizukawa H, Darwish WS, Watanabe KP, Kawai YK, Ishizuka M.Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzy...
Rodríguez-Pozo ML, Armengou L, Monreal L, Viu J, Cesarini C, Jose-Cunilleras E.To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Methods: Experimental study. Methods: Field study. Methods: Ten healthy adult horses. Methods: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor...
Mikhail E, Siccardi E, Bawazir A, Rajesh A, Prathyush S, Al Wazani DMK, Sabeek M, John T.IOX-2 is a potent inhibitor of enzyme prolyl hydroxylases-2 (PHD) that plays a critical role in regulating hypoxia inducible factor (HIF) abundance and oxygen homeostasis. Federation for Equestrian Sports has listed HIF activators as prohibited substances to prevent their usage in doping. Consequently, it became essential to develop adequate knowledge and testing methods to detect it in equine sports drug testing samples. The validated method utilizes ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry in order to detect extremely low concentration of the ...
Keen JA, Hillier C, McGorum BC, Bunton D, Nally JE.Pharmacological evaluation of the unique equine laminar microvasculature is crucial to understanding its role in health and in diseases such as laminitis. However, separating the distinctive characteristics of arterial versus venous components of this complex vascular network has previously proved to be extremely difficult. Encased in a hard hoof capsule, isolation of individual blood vessels presents a considerable challenge. Exacerbating this difficulty, the laminar venous network is adapted to sustain high intravascular pressures and consequently has thickened walls, making the normally str...
Pezzanite LM, Hendrickson DA, Dow S, Stoneback J, Chow L, Krause D, Goodrich L.Antibiotics have been injected intra-articularly by equine veterinarians for decades, either prophylactically when other drugs are administered for osteoarthritis or therapeutically to treat septic arthritis. This route of administration has also more recently gained attention in human orthopaedic clinical practice, particularly as an alternative to systemic antibiotic administration to treat infections following prosthetic arthroplasty. While the rationale for injecting antibiotics intra-articularly has been largely focused on achieving high local drug concentrations, there has been relativel...
Goetz TE, Munsiff IJ, McKiernan BC.The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.0...
Martins FC, Keating SC, Clark-Price SC, Schaeffer DJ, Lascola KM, DiMaio Knych H.To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Boyce M, Malone ED, Anderson LB, Park S, Godden SM, Jenner F, Trumble TN.To determine whether triamcinolone acetonide diffuses from the distal interphalangeal joint (DIPJ) to the navicular bursa, diffusion is direct or systemic, and addition of sodium hyaluronan has an effect on diffusion in horses. Methods: 11 adult horses without forelimb lameness. Methods: 1 randomly chosen forelimb DIPJ of each horse received an injection of 10 mg of triamcinolone acetonide plus 20 mg of sodium hyaluronan (group 1), and the contralateral forelimb DIPJ received an injection of 10 mg of triamcinolone acetonide plus 2 mL of lactated Ringer's solution (group 2). Synovial fluid samp...
Hood DM, Stephens KA, Bowen MJ.Phenoxybenzamine, an alpha adrenergic antagonist, was administered IV to 6 clinically normal horses, 5 horses with experimentally induced diarrhea, and 7 horses with naturally-occurring diarrhea. It was established that a total of 2 mg of phenoxybenzamine/kg of body weight given in divided doses resulted in alpha adrenergic blockage of approximately 72 hours' duration, tranquilization, and mild constipation in the normal horse. The 5 experimental cases of diarrhea were involved in a laminitis research protocol in which laminitis was induced by oral carbohydrate overload. In all 5 of those case...
Bennett RC, Taylor PM, Brearley JC, Johnson CB, Luna SP.This prospective clinical study compared the physiological effects of two commonly used anaesthetic induction techniques in horses maintained with halothane. One hundred horses admitted for elective surgery were randomly allocated to receive either guaiphenesin (to effect) and thiopentone (5 mg/kg), or detomidine (20 microg/kg) and ketamine (2 mg/kg) for the induction of anaesthesia after acepromazine premedication. Anaesthesia was maintained with halothane in oxygen. There were no significant differences in breed, age, sex, weight, type of surgery and duration of anaesthesia between the group...
Sweeney RW, Reef VB, Reimer JM.Nine horses with (naturally acquired) congestive heart failure were treated with 2.2 micrograms of digoxin/kg of body weight by the IV route, followed by 11 micrograms/kg administered orally every 12 hours thereafter. Furosemide was administered IV concurrently with IV administered digoxin every 12 hours. Serum concentration of digoxin was measured after the first (IV) and seventh (orally administered) dose. After IV administration, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase (t1/2 alpha = 0.17 hour), followed by a slower elimination phase (beta ...
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...
McDonnell SM, Odian MJ.This study is a part of our ongoing work toward developing pharmacological methods for enhancing and inducing ejaculation in stallions with ejaculatory dysfunction. We evaluated a combination treatment of imipramine hydrochloride followed 10 minutes later by xylazine hydrochloride for the induction of ex copula ejaculation. Eight pony stallions each underwent 6 treatment trials conducted at 4-day intervals. The trials were conducted in the animals' stalls, where they were observed for 90 minutes following treatment. To evaluate the effect of pretreatment sexual stimulation on the rate of ejacu...
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...
Roger T, Bardon T, Ruckebusch Y.The electrical and mechanical activity of the large intestine and its response to administration of opiate mu and kappa agonists were assessed from electrodes and inductograph coils chronically implanted on the cecocolic segment in six ponies given a diet of hay and concentrates. Before the drugs were given, migrating complexes propagating from the cecum into the colon occurred at the rate of 1.5 to 16/hour. During this propulsive activity, the cecocolic sphincter opened and closed allowing the outflow of cecal contents and preventing the backflow of colic contents. Each pony was used as its o...
Qualls HJ, Holbrook TC, Gilliam LL, Njaa BL, Panciera RJ, Pope CN, Payton ME.The efficacy of orally administered therapeutics for the treatment of cantharidin intoxication has not been evaluated in controlled studies. Objective: To develop a model of acute cantharidin intoxication in laboratory rats and to evaluate in this model the relative efficacy of 3 gastrointestinal therapies used to treat equine cantharidin toxicosis. Methods: Sixty-four male Sprague-Dawley rats. Methods: A blinded, randomized, controlled study was performed on rats surgically implanted with telemetry transmitters for evaluating heart rate, locomotor activity, and body temperature. Orogastric ad...
Gerhards H, Eberhardt C.Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose ...
