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.
Baker A, Plummer CE, Szabo NJ, Barrie KP, Brooks DE.To determine the concentration of doxycycline in preocular tear film following oral administration in horses as a possible therapeutic modality for infectious and keratomalacic equine keratitis. Methods: Eight broodmares without ocular disease from a Thoroughbred breeding facility were included in this study. Each mare received 20 mg/kg of doxycycline by mouth once daily in the morning for five consecutive days. Tears were collected 1 h after doxycycline administration starting on day one of administration and continuing for 10 consecutive days. Doxycycline levels in the tears were measured us...
Thomasy SM, Mama KR, Stanley SD.This study evaluated the validity of measuring fentanyl concentrations in equine plasma using radioimmunoassay (RIA) by comparing it to the established technique of liquid chromatography-mass spectrometry (LC-MS). Equine plasma samples were analyzed using a solid-phase Coat-A-Count fentanyl RIA and a validated LC-MS method. The fentanyl concentrations derived by both methods were compared by linear regression and pharmacokinetic analysis. The cross-reactivity of the primary equine fentanyl metabolite, N-[1-(2-phenethyl-4-piperidinyl)]maloanilinic acid (PMA), with the RIA was determined. The bi...
Sleeper MM, McDonnell SM, Ely JJ, Reef VB.Enalapril is an angiotensin converting enzyme (ACE) inhibitor that is frequently used in human, feline and canine patients with cardiac disease. Its use has been associated with impotence in human patients. The purpose of this study was to evaluate if enalapril (0.5mg/kg PO, q24h) is likely to alter behavior in stallions and to assess its effect on ACE activity at the standard dose used in dogs and cats. Twelve pony stallions were evaluated by physical examination and echocardiography followed by treatment with enalapril (n=6) or placebo (n=6) for 2 months. After one month, blood was drawn and...
Gokbulut C, Cirak VY, Senlik B, Yildirim F, McKellar QA.This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and afte...
Benoit M, Lingen K, Taddei LM, Heffron BT, Hurt L, Lokanc JA, Lingner K, Cardenas E, Flores S, Mayer D, Pilipiak D, Folker-Calderon D, Negrusz A.Pyrilamine (mepyramine) is an H1-receptor antagonist used in human and veterinary medicine. It has the potential to produce central nervous system effects in horses and therefore may have some impact on an outcome of a horse race. A single oral dose of pyrilamine (300 mg/horse) was given to three animals. Serum samples were collected before drug administration and at 0.25, 0.5, 1, 2, 4, 6, 24, 48, 72, 96, 120, and 144 h, and 7, 8, 9, 10, 11, 12, and 13 days post-administration. Urine samples were collected at 0-1, 1-2, 2-4, 4-6, 24, 48, 72, 96, 120, and 144 h, and 7, 8, 9, 10, 11, 12, 13 days ...
Douglas LC, Yi NY, Davis JL, Salmon JH, Gilger BC.In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-i...
Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M.Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and,...
Goudah A, Abo El-Sooud K, Shim JH, Shin HC, Abd El-Aty AM.The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were...
Camargo FC, Robinson NE, Dirikolu L, Berney C, Eberhart S, Derksen FJ, Lehner AF, May J, Hughes C, Tobin T.Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD.To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma ...
Parlevliet JM, Paccamonti DL, Barker SA.This study was conducted to measure the concentration of cefquinome in the endometrium of mares after intrauterine treatment and to evaluate associated inflammation. Mares (n = 14) were randomly assigned to one of the following groups: (i) control (n = 4) were either not treated (n = 2) or received (n = 2) lactated Ringer's intrauterine for 1 or 3 days; (ii) treated mares (n = 10) received intrauterine cefquinome for 1 or 3 days. After at least 10 days had passed following the last treatment and ovulation, mares were given Prostaglandin F2alpha (PGF2alpha) and were randomly assigned to an alte...
Kearns CF, McKeever KH.Clenbuterol is a beta(2)-agonist and potent selective bronchodilator that is used to treat bronchospasm in the horse. The drug is normally administered to horses orally as a syrup formulation. Once absorbed into the systemic circulation, clenbuterol has the potential to cause many side effects, including a repartitioning effect and major alterations in cardiac and skeletal muscle function. Recent studies have also reported that clenbuterol can affect bone and the immune, endocrine and reproductive systems. A great deal of information has been published on the beneficial effects of short term t...
Luna SP, Angeli AL, Ferreira CL, Lettry V, Scognamillo-Szabó M.Pharmacopuncture, the injection of subclinical doses of drugs into acupoints reduces drug undesirable side effects, residues in animal consumption products and treatment costs in large animals. Acepromazine (Acp) produces several undesirable effects, such as hypotension. Previous studies with the injection of 1/10 of Acp dose in dog acupoints showed its advantage for sedation, minimizing undesirable effects. Eight horses were randomly submitted to four different treatment protocols according to a Latin Square double-blind design: (i) 0.1 ml kg(-1) of saline subcutaneously injected at the cervi...
Arguedas MG, Hines MT, Papich MG, Farnsworth KD, Sellon DC.Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available. Objective: The purpose of this study was to determine the PK of butorphanol in neonatal foals after IV and IM administration; to determine whether administration of butorphanol results in physiologic or behavioral changes in neonatal foals; and to describe adverse effects associated with its use in neonatal foals. Methods: Six healthy mixed breed pony foals between 3 and 12 days of age were used. Methods: In a 3-way crossover design, foals received ...
Maes A, Garré B, Desmet N, van der Meulen K, Nauwynck H, De Backer P, Croubels S.Two methods are presented for the determination of 'respectively' the plasma protein unbound and total concentration of acyclovir in horse plasma and body fluids: first, a liquid-liquid extraction was performed on plasma, combined with HPLC-fluorescence detection for the total plasma concentration; second a more sensitive method using high-performance liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) was described for plasma and for body fluids analysis. To obtain the unbound concentration of acyclovir in plasma, a simple deproteinizati...
Maher O, Nieto JE, Stanley SD, Dore E, Snyder JR.To determine the effect of ranitidine on gastric emptying in horses. Methods: 11 adult horses. Methods: In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (...
Davidson GS.Anesthetization of large animals, such as the horse, is a challenge for veterinarians and compounding pharmacists. This article discusses the technique of intravenous anesthesia by using a combination of xylazine and ketamine in the horse for short-term unconsciousness; a combination of xylazine, diazepam, and ketamine, for improved sedation and muscle relaxation; and a combination of xylazine, ketamine, and guaifenesin, referred to as Triple Drip, for the maximum 1-hour duration of unconsciousness. Compounding pharmacists that have the facilities and training required to prepare sterile compo...
Okamura K, Sasaki N, Yamada M, Yamada H, Inokuma H.Although extensive work has been done to elucidate the beneficial and unfavorable effects of gastrointestinal prokinetic agents in humans, little is known on the effects of these agents in horses. In this study, we compared the effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric emptying, jejunal and caecal motility and evaluated these agents' adverse drug reactions (ADRs). Methods: Seven healthy adult Thoroughbreds. Methods: Mosapride 1.0mg/kg and 2.0mg/kg, metoclopramide 0.2mg/kg, and cisapride 1.0mg/kg were dissolved in 100mL distilled water for oral administrat...
Meulyzer M, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S.To compare synovial glucosamine levels in normal and inflamed equine joints following oral glucosamine administration and to determine whether single dose administration alters standard synovial parameters of inflammation. Methods: Eight adult horses were studied. On weeks 1 and 2, all horses received 20mg/kg glucosamine hydrochloride by nasogastric (NG) intubation or intravenous injection. On weeks 3 and 4, 12h after injection of both radiocarpal joints with 0.25 ng Escherichia coli lipopolysaccharide (LPS) to induce inflammation, glucosamine hydrochloride or a placebo was administered by NG ...
Fidani M, Gamberini MC, Pasello E, Palazzoli F, Dimasi T, Montana M.A development of a rapid and sensitive LC-MS/MS method for the simultaneous detection of active ingredients of the euthanasic veterinarian drug Tanax mixture is described. The method proposed, with a retention time of few minutes (6 min) was developed for an equine serum sample with solid-phase extraction (S.P.E). This S.P.E. procedure has been revealed useful for the determination of very low concentrations of Tanax analytes (0.05-1 ng/ml). The method was validated in terms of specificity/selectivity, sensitivity, recovery and precision.
Maxwell LK, Bentz BG, Bourne DW, Erkert RS.Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7-11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7-34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance li...
Zozaya DH, Gutiérrez OL, Ocampo CL, Sumano LH.Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C(S0)) was 112.21 +/- 1.27 microg/mL and 201.43 +/- 1.56 microg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC(90)) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obt...
Okamura K, Sasaki N, Fukunaka M, Yamada H, Inokuma H.The prokinetic effect of the 5-HT4 receptor agonist mosapride was evaluated in seven healthy thoroughbreds. Mosapride was orally administered at doses of 0.5, 1.0 or 1.5 mg/kg. The breath 13CO2/12CO2 rate (Delta13CO2), an indirect indicator for the rate of gastric emptying, was measured at appropriate points for 4 hr after drug administration. There was a significant increase compared with the control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165 min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric emptying in horses.
Braim AE, Macdonald MH, Bruss ML, Stanley SD, Giri JK, Giri SN.To characterize the plasma pharmacokinetics and clinical effects of pirfenidone administered IV in healthy horses. Methods: 6 adult horses. Methods: A 15 mg/kg dose of pirfenidone was administered IV over 5 minutes. Physical variables were recorded and blood samples collected prior to infusion; 2.5 minutes after beginning infusion; at the end of infusion; and at 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after completion of infusion. Plasma concentrations of pirfenidone and its metabolites were determined. Results: Mild clinical effects...
Durham AE, Rendle DI, Newton JE.Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. Objective: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. Methods: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sen...
Raidal SL, Edwards S.To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. Methods: Twelve adult Standardbred and Thoroughbred mares. Methods: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of con...
Peterbauer C, Larenza PM, Knobloch M, Theurillat R, Thormann W, Mevissen M, Spadavecchia C.To investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies. Methods: Prospective, blinded, cross-over study. Methods: Six healthy 5-year-old Shetland ponies. Methods: Ponies received either 0.6 mg kg(-1) racemic ketamine (group RS) or 0.3 mg kg(-1) S-ketamine (group S) intravenously (IV), followed by a CRI of 20 microg kg(-1)minute(-1) racemic ketamine (group RS) or 10 microg kg(-1)minute(-1) S-ketamine (group S) for 59 minutes. The NWR was evoked by trans...
Soma LR, Rudy JA, Uboh CE, Xu F, Snapp HM.To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses. Methods: 7 Thoroughbreds. Methods: In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography- mass spectrometry. Results: Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of alpha, beta, and gamma half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Tot...
Caprile KA, Short CR.Rational drug therapy in the foal requires a sound knowledge of the pharmacodynamics and pharmacokinetics of various drugs as well as a thorough understanding of the physiologic differences that exist between the neonate and the adult and that may serve to alter drug disposition and, therefore, drug response. A summary of these physiologic factors with emphasis on the foal is presented and is followed by recommendations regarding the applied therapeutics of various antimicrobial agents.
Thomas AD, Bowater IC, Vine JH, McLean JG.To determine whether a drug detected in the blood or urine of a racing animal could have penetrated through the skin from a topically applied preparation. Methods: Blood and urine of dogs and horses were analysed after topical administration of three common nonsteroidal anti-inflammatory preparations. Methods: Dimethylsulphoxide was analysed using a gas chromatograph with a flame photometric detector. Phenylbutazone, its metabolites and lignocaine were analysed using a gas chromatograph with a mass selective detector. Results: Dimethylsulphoxide, phenylbutazone and lignocaine were detected in ...
Liu Y, Uboh CE, Li X, Guan F, You Y, Maylin GA, Zhu F, Soma LR.A rapid and sensitive method for simultaneous screening, quantification and confirmation of 17 barbiturates in horse plasma using liquid chromatography-tandem mass spectrometry is described. Analytes were recovered from plasma by liquid-liquid extraction using methyl tert-butyl ether, separated on a C18 column, and analyzed in negative electrospray ionization mode. Multiple-reaction monitoring was employed for screening and quantification. Confirmation for the presence of the analytes was achieved by comparing ion intensity ratio. The ranges for limits of detection, quantification and confirma...
Claunch KM, Eggleston RB, Baxter GM.To compare the effects of 2 approaches and 2 injection volumes on diffusion of mepivacaine hydrochloride for local analgesia of the deep branch of the lateral plantar nerve (DBLPN) in horses. Methods: Experimental study. Methods: 16 adult horses. Methods: Either 2 mL (low volume) or 8 mL (high volume) of mepivacaine hydrochloride-iohexol (50:50 mixture) was injected by means of 1 of 2 techniques to produce analgesia of the DBLPN. For technique 1, the needle was inserted 15 mm distal to the head of the fourth metatarsal bone and directed perpendicular to the limb. For technique 2, the needle wa...
Dockalova H, Zeman L, Baholet D, Batik A, Skalickova S, Horky P.Milk thistle seeds contain a mixture of flavonoids known as silymarin, which consists of silybin, isosilybin, silychristine, and silydianin. Until now, there has been no evidence of monitoring the digestibility of silymarin complex in horses. The aim of the research was to evaluate the digestibility of silymarin complex and the effect of nutrient digestibility in horses. Different daily feed doses (FD) of milk thistle expeller (0 g, 100 g, 200 g, 400 g, 700 g) were administered to five mares kept under the same conditions and at the same feed rations. Digestibility of silymarin complex was mon...
Giorgi M, Cuniberti B, Ye G, Barbero R, Sgorbini M, Vercelli C, Corazza M, Re G.Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasm...
Valente AC, Brosnan RJ, Guedes AG.To evaluate pharmacokinetics, recovery times, and recovery quality in horses anesthetized with 1.2 times the minimum alveolar concentration of sevoflurane or desflurane. Methods: 6 healthy adult horses. Methods: Anesthesia was maintained with sevoflurane or desflurane for 2 hours at 1.2 times the minimum alveolar concentration. Horses recovered without assistance. During recovery, end-tidal gas samples were collected until horses spontaneously moved. Anesthetic concentrations were measured by use of gas chromatography. After a 1-week washout period, horses were anesthetized with the other inha...
Lerch M, Allbaugh RA, Sebbag L, Mochel JP, Weller P, Borts DJ.Paper spray high-resolution accurate mass spectrometry is a fast and versatile analysis method. This ambient ionization technique enables the quantitation of xenobiotics in complex biological matrices without chromatography or conventional sample extraction. The simplicity, rapidity, and affordability of the paper spray mass spectrometry (PS-MS) method make the technique especially attractive for clinical investigations where fast and affordable sample analysis is crucial. A new PS-MS method for the quantitation of voriconazole in equine tears was developed and validated. For a concentration r...
Kempchen S, Kuhn M, Spadavecchia C, Levionnois OL.To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. Methods: Prospective, randomized, blinded clinical trial. Methods: Forty horses undergoing elective surgery. Methods: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received ...
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...
Buchner HH, Kübber P, Zohmann E, Peham C.A kinematic study was performed to establish the locomotion pattern of horses under detomidine sedation and the effects of antagonization for possible use during lameness examinations in uncooperative horses. The kinematics of 17 Warmblood horses (9 sound, 8 lame with chronic forelimb lameness) were recorded on 2 days using a high-speed video system while trotting (3.9 m/s) on a treadmill. On each day a control measurement was carried out prior to sedation with detomidine (10 micrograms/kg bwt) and repeated recordings at 15, 25, 35, 45 and 60 min after sedation. On the second day, sedation was...
Davis JL, Marshall JF, Papich MG, Blikslager AT, Campbell NB.The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half-life (t(...
Soma LR, Uboh CE, Guan F, Luo Y, Teleis D, Runbo L, Birks EK, Tsang DS, Habecker P.Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)...
Rees WA, Harkins JD, Lu M, Holland RE, Lehner AF, Tobin T, Chambers TM.To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. Methods: 5 clinically normal horses and 8 horses seronegative to influenza A. Methods: Horses were given rimantadine (7 mg/kg of body weight, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, p.o., q 1...
Knych HK, Stucker K, Gretler SR, Kass PH, McKemie DS.In humans, codeine is a commonly prescribed analgesic that produces its therapeutic effect largely through metabolism to morphine. In some species, analgesic effects of morphine have also been attributed to the morphine-6-glucuronide (M6G) metabolite. Although an effective analgesic, administration of morphine to horses produces dose-dependent neuroexcitation at therapeutic doses. Oral administration of codeine at a dose of 0.6 mg/kg has been shown to generate morphine and M6G concentrations comparable to that observed following administration of clinically effective doses of morphine, witho...
Pakkanen SAE, de Vries A, Raekallio MR, Mykkänen AK, Palviainen MJ, Sankari SM, Vainio OM.Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent th...
Kendall A, Mosley C, Bröjer J.Signs of tachypnea after sedation of febrile horses with alpha2-agonists have been noted previously but have not been further investigated. Objective: To examine the effects of xylazine and detomidine on respiratory rate and rectal temperature in febrile horses and to investigate if either drug would be less likely than the other to cause changes in these variables. Methods: Nine febrile horses and 9 healthy horses were included in the study. Methods: Horses were randomly assigned to sedation with xylazine 0.5 mg/kg or detomidine 0.01 mg/kg. Heart rate and respiratory rate were recorded before...
Lester GD, Merritt AM, Neuwirth L, Vetro-Widenhouse T, Steible C, Rice B.To determine the effect of erythromycin lactobionate (ERY) on ileocecocolic myoelectric activity and passage of radiolabeled markers from the cecum. Methods: 6 healthy adult ponies. Methods: After a 12-hour nonfeeding period, 370 MBq of technetium 99m-labeled sulfur colloid in egg albumen and 37 MBq of indium 111-labeled diethyltriaminepentaacetic acid in 60 ml of water were administered directly into the cecal apex. The following drug concentrations were tested: ERY, 0.01, 0.10, 1.0, and 10.0 mg/kg of body weight; ERY, 0.10 mg/kg bolus; and saline (0.9% NaCl) solution, 10 ml. All treatments, ...
Swain EA, Magdesian KG, Kass PH, Edman JE, Knych HK.Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics wi...
van Hoogmoed LM, Boscan PL.Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. Objective: To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. Methods: Using circular smooth ...
Brown MP, Gronwall RR, Houston AE.Six healthy adult mares were each given an oral loading dose of ormetoprim(OMP)-sulfadimethoxine (SDM) at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg, followed by four maintenance doses of 4.6 mg of OMP/kg and 22.9 mg of SDM/kg, at 24 h intervals. Ormetoprim and SDM concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid, urine and endometrium. The highest mean serum OMP concentration was 0.92 micrograms/mL 0.5 h after the first dose; the highest mean SDM concentration was 80.9 micrograms/mL 8 h after the first dose. The highest mean synovial fluid c...
Wijekoon S, Tsogbadrakh M, Sunaga T, Wang Y, Mwale C, Kim S, Alimaa D, Okumura M.The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in to two-groups; one group was treated with a PPS once a week for 4-weeks while another group keeping as placebo. Blood samples at day 0 (D0), before race (BR; day 28) and after race (AR; day 28) were analyzed for serum biochemistry, hepcidin and iron concentrations. Significant reduction of hepcidin was observed at AR in PPS group when compared with BR placebo (P<0.05) and AR placebo (P<0.01). Mean hepcidin concentration differ...
Westermeyer HD, Hendrix DV, Ward DA, Cox SK.To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses. Methods: 24 ophthalmologically normal adult horses. Methods: 0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, r...
Duran SH, Ravis WR, Pedersoli WM, Schumacher J.Pharmacokinetics of phenobarbital was examined in 6 mature horses after 12 mg of phenobarbital/kg of body weight was infused over 20 minutes. Biexponential decrease in serum phenobarbital concentrations was observed with a distribution-phase half-life of 0.101 +/- 0.086 hour (mean +/- SD) and a terminal-phase elimination half-life of 18.3 +/- 3.65 hours. The volume of distribution at steady state was 0.803 +/- 0.070 L/kg. Total body clearance of phenobarbital was 30.8 +/- 6.2 ml/h/kg. The high clearance in the horse seems to explain the markedly shorter half-life of phenobarbital in this speci...
Dembek KA, Hurcombe SD, Schober KE, Toribio RE.To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. Methods: An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. Conclusions: Atrial fibrillation is the most commonly diagnosed dysrhythmia ...
Slocombe JO, McCraw BM.Four pony foals were inoculated with Strongylus edentatus infective larvae and on days 3 and 4 postinfection two of the ponies were treated with thiabendazole, each at the rate of 440 mg/kg of body weight. Total circulating eosinophil counts in untreated ponies increased to over 1700 per cu mm after the second week postinfection. In the treated ponies as well as in an uninfected untreated pony eosinophil counts did not increase beyond 100 per cu mm. At necropsy on day 35 postinfection the cecum, colon and omentum of treated ponies were normal and few tracks were present on the surface of the l...
King JN, Gerring EL.Dopamine was infused intravenously (1, 5 and 10 micrograms/kg/min) for 60 min in three fasted ponies. A dose-dependent increase in heart rate occurred that was rapid in onset and termination at the start and end of the infusions, respectively. Dose-dependent changes in gastric and small intestinal motility were observed. An initial marked inhibition of gastric contraction amplitude was followed by a secondary prolonged period of activity. At the same time the small intestine showed a prolonged period of irregular activity (phase II) and a marked increase in the interval between successive phas...
Mathes RL, Reber AJ, Hurley DJ, Dietrich UM.To evaluate the effects of topical antifungal drugs and delivery vehicles on the morphology and proliferation rate of cultured equine keratocytes. Methods: 16 corneas obtained from 8 apparently ophthalmologically normal horses < 0.5 hours after euthanasia for reasons unrelated to the study. Methods: Primary cultures of equine keratocytes were obtained from corneal stroma and were exposed to several concentrations of 3 commonly used, topically applied antifungals: natamycin, itraconazole, and miconazole. In addition, effects of drug delivery vehicles DMSO, benzalkonium chloride, and carboxym...
Jouvel C, Maciejewski P, Garcia P, Bonnaire Y, Horning S, Popot MA.A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the ne...
Wieder ME, Paine SW, Hincks PR, Pearce CM, Scarth J, Hillyer L.Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post l...
