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.
Mayinda GD, Serreau D, Gesbert A, Reigner F, Sutra JF, Lespine A, Sallé G.The management of equine strongyles has become problematic over the last decade because of an increased prevalence of drug-resistant isolates worldwide. Therapeutic options are therefore limited, leaving macrocyclic lactones as the most often effective drug class. However, their lipophilic properties result in a long-lasting elimination that could favour drug resistance selection. As a result, ivermectin treatment in lactating mares could promote suboptimal exposure of their foal parasites to ivermectin, thereby selecting for more resistant worms. To test for this putative transfer, we selecte...
Watanabe R, Huruta H, Ueno Y, Nukada T, Niwa H, Shinyashiki N, Kano R.Luliconazole (LCZ) is an imidazole antifungal medication that exhibits excellent activity against dermatophytes. As a topical cream and lotion (approved for human use), LCZ has demonstrated a broad spectrum of activity against human dermatophytoses. Objective: This is the first study to investigate the in vitro susceptibility of clinical isolates from horse dermatophytoses to LCZ. Methods: No animals were used in this study. Methods: In the present study, the in vitro susceptibilities of clinical isolates of dermatophytes to LCZ, clotrimazole (CTZ), miconazole (MCZ) and terbinafine (TRF) wer...
Knych HK, Arthur RM, Gretler SR, McKemie DS, Goldin S, Kass PH.Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post-administration. Serum for determination of thromboxane concentrations and whole blood samp...
Neudeck S, Twele L, Kopp V, Kästner S.The aim was to determine the effects of vatinoxan on dexmedetomidine plasma concentrations and effects on cardiovascular and intestinal tissue pharmacodynamics. In a prospective randomized study, six horses were premedicated intravenously with dexmedetomidine 3.5 µg kg followed by a constant-rate infusion of 7 µg kg h (group DEX) and six horses with dexmedetomidine of the same dose (bolus and constant-rate infusion) combined with vatinoxan 130 µg kg followed by 40 µg kg h (group VAT). Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane. Venous bloo...
Willette C, Aarnes TK, Lerche P, Ricco-Pereira C, Ballash GA, Bednarski RM.To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. Methods: Randomized, blinded, three-way crossover prospective design. Methods: A total of eight healthy adult horses weighing 470-575 kg. Methods: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg), ketamine (1 mg kg) and detomidine (0.04 mg kg) (treatment TKD); ketamine (3 mg kg) and detomidine (0.04 mg kg) (treatment KD); and tiletamine-zolazepam (2.4 mg ...
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...
Schenk I, Machnik M, Broussou D, Meuly A, Roques BB, Lallemand E, Düe M, Röttgen H, Lagershausen H, Toutain PL, Thevis M.In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (...
Chapuis RJJ, Smith JS, Uehlinger FD, Meachem M, Johnson R, Dowling PM.The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was samp...
Wallace GE, McKaba VF, Reinhart JM, Li Z, Austin S, Fries RC.Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liq...
Knych HK, McKemie DS, Kanarr KL, White SD.To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. Methods: 12 healthy adult horses. Methods: In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg...
Sandbaumhüter FA, Gittel C, Larenza-Menzies MP, Theurillat R, Thormann W, Braun C.The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l-methadone and d-methadone and their major metabolites, l- and d-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection from...
Raisis AL, Mosing M, Hosgood GL, Secombe CJ, Adler A, Waldmann AD.Electrical impedance tomography (EIT) provides clinically useful lung images; however, it would be an advantage to extract additional cardiovascular information from the data. The aim of this study was to evaluate if cardiac-related changes measured by EIT can be used to measure pulse rate (PR) under physiological as well as high and low blood pressure states in anaesthetised horses. Electrical impedance tomography data and PR from seven horses anaesthetised in dorsal recumbency were recorded over 1 min during mechanical ventilation and 1 min of apnoea. Data were collected at four measurement ...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Ahmad WA, Prince H, Kelmer G. The aim of this study was to determine the concentration of metronidazole in the distal interphalangeal joint (DIPJ) of the thoracic limb after administering metronidazole to standing horses by intravenous regional limb perfusion (IVRLP). Methods: Eleven healthy horses had a wide rubber tourniquet applied to the proximal aspect of the antebrachium for 0.5 hours and 500 mg of metronidazole diluted in physiologic saline solution to a total volume of 108 mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 ...
Bessonnat A, Vanore M.Evaluate the effect of repeated doses of topical 1% cyclopentolate hydrochloride alone and in combination with topical 2.5% phenylephrine on pupil diameter (PD), tear production (STT-1), intraocular pressure (IOP), digestive function (gut motility and feces production), and heart rate (HR). Methods: Six healthy mares. Methods: In a prospective, randomized, controlled, and crossover design study, the left eye of six healthy mares was administered 0.2 mL of cyclopentolate alone and in combination with 0.2 mL of phenylephrine. The drugs were administered 3 times a day for 1 day, twice a day fo...
Stewart HL, Engiles JB, Richardson DW, Levine DG.To describe the bactericidal and fungicidal properties of a 0.0005% chlorhexidine (CHD) solution potentiated with EDTA-Tris buffers (CHD-EDTA-Tris) and evaluate the safety of 0.0005% CHD-EDTA-Tris in the upper respiratory tract (URT) of normal horses. Methods: Clinical, prospective study. Methods: Eight healthy, skeletally mature horses. Methods: In vitro-serial dilutions of CHD-EDTA-Tris and EDTA-Tris alone were evaluated for bactericidal and fungicidal activity against Aspergillus fumigatus, Escherichia coli, Staphylococcus aureus, Streptococcus equi subspecies ssp. equi, Streptococcus equi ...
Ström L, Dalin F, Domberg M, Stenlund C, Bondesson U, Hedeland M, Toutain PL, Ekstrand C.Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. Results: Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and t...
Natalini CC, Paes SD, Polydoro ADS.The study aim is to compare the effects of epidural administration of two different doses of romifidine combined with morphine in horses. A prospective crossover blinded experimental design was used. Five adult healthy horses two males and three females with a mean body weight of 380 ± 45 Kg (335-425 kg), were studied. Treatments consisted of romifidine 30 μg/kg (R30) or 60 μg/kg (R60) combined with morphine 0.1 mg/kg with a washout interval of 72 hours, administered through an epidural catheter placed at the first intercoccygeal space. Heart rate (HR) and respiratory rate (f), pH, blood ga...
de Wasseige S, Picotte K, Lavoie JP.A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a different nebulizer, lack of efficacy and cortisol suppression were observed. Objective: Nebulized dexamethasone is as effective as PO administration for the treatment of severe asthma in horses. Methods: Twelve horses with severe asthma from a research herd. Methods: Randomized clinical trial. Horses were divided into 2 groups and received 5 mg of dexamethasone sodium phosphate by nebulization using a Flexineb mask (NE, n = 6)...
Lawless SP, Moorman VJ, Hendrickson DA, Mama KR.To compare efficacy and safety of a continuous rate infusion of detomidine hydrochloride and romifidine hydrochloride for standing elective bilateral laparoscopic ovariectomy in mares. Methods: Blinded, randomized prospective clinical study. Methods: Eighteen healthy mares presenting for elective bilateral ovariectomy METHODS: Mares were randomly assigned to one of two sedation protocols. Prior to surgery, baseline head height, heart rate, respiratory rate, and postural sway were recorded. An IV loading dose of α2-agonist (46 μg/kg romifidine or 13.9 μg/kg detomidine) was administered. S...
Ryan D, McKemie DS, Kass PH, Puschner B, Knych HK.The increasing availability of cannabidiol (CBD) and anecdotal reports of its anti-inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD...
Crabtree NE, Epstein KL.Despite the frequent inclusion of fluid therapy in the treatment of many conditions in horses, there are limited studies available to provide evidenced-based, species-specific recommendations. Thus, equine fluid therapy is based on the application of physiology and extrapolation from evidence in other veterinary species and human medicine. The physiologic principles that underly the use of fluids in medicine are, at first glance, straightforward and simple to understand. However, in the past 20 years, multiple studies in human medicine have shown that creating recommendations based on theory i...
Mosichuk AP, Smith JS, Tatarniuk DM, Troy JR, Kreuder AJ.Septic synovitis is a critical orthopedic condition in horses. Early intervention is key, with antibiotic therapy typically initiated prior to culture and susceptibility reports becoming available. The pharmacokinetics of several antibiotics have been studied in horses for use in intravenous regional limb perfusion (IVRLP) for septic synovitis, including the carbapenem antibiotic, meropenem. For a variety of factors, some veterinary clinicians may select IVRLP meropenem as therapy for these cases. Meropenem is a vital antibiotic in human medicine, making veterinary use divisive. However, verif...
Flynn H, Cenani A, Brosnan RJ, DiMaio Knych HK, de Araujo Aguiar AJ.To determine the pharmacokinetics and pharmacodynamics of high-concentration formulation of buprenorphine (1.8 mg mL; Simbadol) following subcutaneous (SC) administration in horses. Methods: Prospective, randomized, crossover trial. Methods: A group of six healthy adult horses weighing 521-602 kg. Methods: On three occasions, Simbadol (0.005 mg kg; treatment S5), (0.0025 mg kg; treatment S2.5) or saline (treatment SAL) were administered SC at least 7 days apart in random order. Electrical nociceptive threshold (ENT) measured on the neck region, physiologic variables, locomotor activity, degree...
Leventhal HR, McKenzie HC, Estell K, Council-Troche M, Davis JL.The objective of this study was to determine the pharmacokinetics and tolerability of tulathromycin (Draxxin ; 2.5 mg/kg once) after intramuscular (IM), subcutaneous (SC), and slow intravenous (IV) administration to six adult horses. A three-phase design and 4-week washout period were used. Drug concentrations in blood and bronchoalveolar lavage (BAL) samples were determined by ultra-performance liquid chromatography tandem mass spectrometry and pharmacokinetic parameters calculated using noncompartmental analysis. Following SC and IM administration, all horses exhibited sweating, discomfort,...
Skrzypczak H, Reed R, Brainard B, Sakai D, Barletta M, Quandt J, Smyth C, Ruch M, Knych H.Matrix fentanyl patches have not been investigated in horses and may represent an effective means of providing analgesia over an extended time period without venous catheterisation. Objective: To describe the pharmacokinetics of a matrix transdermal fentanyl patch in horses. Methods: Randomised experiment, Latin-square design. Methods: Six adult horses were given each of three treatments with a 96-hour washout. For each treatment, two 100 µg/h matrix fentanyl patches were applied to the inguinal region (TXA), metacarpus (TXM) or ventral tail base (TXT) for 72 hours. Blood samples for fentan...
Knych HK, Magdesian KG.Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence-based clinical decision-making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra-label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. P...
Mathew B, Philip M, Perwad Z, Karatt TK, Caveney MR, Subhahar MB, Karakka Kal AK.Hypoxia-inducible factor (HIF) stabilizer belongs to a novel class of pharmacologically active substances, which are capable of inducing the endogenous erythropoietic system. The transcriptional activator HIF has been shown to significantly increase blood hemoglobin and is well set for the treatment of anemia resulting from chronic kidney disease. This research work reports a comprehensive study of the most popular HIF stabilizer roxadustat and its metabolites in thoroughbred horse urine after oral administration. The plausible structures of the detected metabolites were postulated using liqui...
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...
Darby S, Sanchez LC, Mallicote MF, House AM, Plummer CE, Nadruz V, Benmoha RH, Roberts SM, Derendorf H, Silva-Sanchez C, Claire J, MacKay RJ.Creeping indigo (Indigofera spicata) toxicosis is an emerging problem among horses in Florida and bordering states. Objective: To quantify the putative toxins l-indospicine (IND) and 3-nitropropionic acid (NPA) in creeping indigo collected from multiple sites and to measure plasma toxin concentrations in ponies fed creeping indigo and horses with presumptive creeping indigo toxicosis. Methods: Experimental descriptive study with descriptive observational field investigation. Methods: Air-dried creeping indigo was assayed for IND and NPA content. Five ponies were fed chopped creeping indigo con...
Gretler SR, Finno CJ, Kass PH, Knych HK.In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences in the metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The objective of this study was to phenotype a population of 100 horses from five different breeds and assess differences in the metabolic activity of the equine CYP2D6 homolog using codeine as a probe drug. Administration of a probe drug is a common method used for patient phenotyping in human medicine, whereby the ratio of parent drug to metabolite (metabolic ratio, MR) can be used to compare relative enzym...
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 ...
Schramme AR, Pinto CR, Davis J, Whisnant CS, Whitacre MD.Current therapy protocols to treat persistent post mating endometritis and retained fetal membranes in mares typically include the administration of ecbolic drugs. Evaluation of the pharmacokinetics and tolerability of carbetocin, a long-acting oxytocin analogue, after i.v. administration is required. Objective: To determine the pharmacokinetic parameters (principally half-life) of carbetocin in horses. Methods: Five mature mares and one gelding received 0.175 mg carbetocin i.v. All animals were monitored periodically throughout the study for elevation in rectal temperature, heart rate, respir...
Davis JL, Little D, Blikslager AT, Papich MG.Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro/in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioava...
Martens RJ, Mealey K, Cohen ND, Harrington JR, Chaffin MK, Taylor RJ, Bernstein LR.To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals. Methods: 6 healthy neonatal foals. Methods: Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy. Results: Mean +/- SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 +/- 311 ng/mL; time to peak serum concentra...
Mössner LD, Schmitz A, Theurillat R, Thormann W, Mevissen M.To identify and characterize cytochrome P450 enzymes (CYPs) responsible for the metabolism of racemic ketamine in 3 mammalian species in vitro by use of chemical inhibitors and antibodies. Methods: Human, canine, and equine liver microsomes and human single CYP3A4 and CYP2C9 and their canine orthologs. Methods: Chemical inhibitors selective for human CYP enzymes and anti-CYP antibodies were incubated with racemic ketamine and liver microsomes or specific CYPs. Ketamine N-demethylation to norketamine was determined via enantioselective capillary electrophoresis. Results: The general CYP inhibit...
Driessen B, Nann L, Benton R, Boston R.To study whether hemodynamic function in horses, particularly mean arterial blood pressure (MAP), is better maintained with sevoflurane than isoflurane, thus requiring less pharmacological support. Methods: Prospective randomized clinical investigation. Animals Thirty-nine racehorses undergoing arthroscopy in lateral recumbency. Methods: Horses were assigned to receive either isoflurane (n = 20) or sevoflurane (n = 19) at 0.9-1.0 minimum alveolar concentration (MAC) for maintenance of anesthesia. Besides routine clinical monitoring, cardiac output (CO) was measured by lithium dilution. Hemodyn...
Zielinski K, Sekula B, Bujacz A, Szymczak I.Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three pro...
Enderle AK, Levionnois OL, Kuhn M, Schatzmann U.To compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses. Methods: Prospective, randomized, blinded clinical trial. Methods: Forty horses (ASA I-III) undergoing elective surgery. Methods: Horses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI ...
Williams DC, Aleman MR, Brosnan RJ, Fletcher DJ, Holliday TA, Tharp B, Kass PH, Steffey EP, LeCouteur RA.Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. Objective: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. Methods: Six healthy horses. Methods: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded d...
Sykes BW, Underwood C, McGowan CM, Mills PC.The objectives were to document the pharmacokinetics of intravenous, enteric-coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric-coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fasted state (ECO-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fed state (ECO-Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL-Fasted). Plasma omeprazole concentrations were det...
Du J, White N, Eddington ND.The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion. Methods: Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. ...
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were ...
Greene SA, Thurmon JC, Tranquilli WJ, Benson GJ.Eight ponies were anesthetized with a solution containing 50 mg of guaifenesin, 1 mg of ketamine, and 0.5 mg of xylazine X ml-1 of 5% dextrose in water. Anesthesia was induced by IV injection (1.1 ml X kg-1), followed by continuous IV infusion at 2.75 ml X kg-1 X hr-1. Heart rate, rate-pressure product, mean pulmonary artery pressure, and standard bicarbonate were not significantly changed throughout the study. Systolic, diastolic, and mean arterial pressures and left ventricular stroke work index were significantly decreased at 5 and 15 minutes after a bolus of the anesthetic solution was inj...
Chan GH, Ho EN, Leung DK, Wong KS, Wan TS.The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast...
Steffey EP, Mama KR, Galey FD, Puschner B, Woliner MJ.To quantitate effects of dose of sevoflurane and mode of ventilation on cardiovascular and respiratory function in horses and identify changes in serum biochemical values associated with sevoflurane anesthesia. Methods: 6 healthy adult horses. Methods: Horses were anesthetized twice: first, to determine the minimum alveolar concentration (MAC) of sevoflurane and second, to characterize cardiopulmonary and serum biochemical responses of horses to 1.0, 1.5, and 1.75 MAC multiples of sevoflurane during controlled and spontaneous ventilation. Results-Mean (+/- SEM) MAC of sevoflurane was 2.84 +/- ...
Meyer S, Giguère S, Rodriguez R, Zielinski RJ, Grover GS, Brown SA.The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six...
Steffey EP, Eisele JH, Baggot JD.To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO. Methods: 6 adult horses. Methods: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). ...
Schnepf A, Bienert-Zeit A, Ertugrul H, Wagels R, Werner N, Hartmann M, Feige K, Kreienbrock L.The usage of antimicrobial drugs (AMs) leads to an increase in antimicrobial resistance (AMR). Although different antimicrobial usage (AMU) monitoring programs exist for livestock animals in Germany, there is no such system for horses. However, with the increasing usage of electronic practice management software (EPMS), it is possible to analyze electronic field data generated for routine purposes. The aim of this study was to generate AMU data for German horses with data from the Clinic for Horses (CfH), University of Veterinary Medicine Hannover (TiHo), and in addition to show that different...
Muir WW, Sams RA, Huffman RH, Noonan JS.The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted ...
Butt TD, Bailey JV, Dowling PM, Fretz PB.The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion. The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion. A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin. Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath. The tourniquet was remov...
Martinez M, Modric S.In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter...
Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N.Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allog...
Merritt AM, Burrow JA, Hartless CS.To evaluate the effect on equine duodenal motility of some analgesic agents commonly used to treat colic. Methods: 4 healthy adult healthy horses--2 mares and 2 geldings--which were carrying an indwelling gastric cannula made of silastic rubber. One horse also carried 2 long-term indwelling bipolar electrodes that had been sutured onto the duodenum and jejunum. Methods: To ensure an empty stomach, solid food was withheld from horses for around 20 hours prior to an experiment. Using videoendoscopic guidance, an 8-F catheter with 3 small, discrete pressure sensors was passed through the gastric ...
Regan FH, Hockenhull J, Pritchard JC, Waterman-Pearson AE, Whay HR.To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. Objective: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Methods: Observer-blinded, placebo-controlled trial. Methods: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20...
Soma LR, Uboh CE, Liu Y, Li X, Robinson MA, Boston RC, Colahan PT.This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9...
Secombe CJ, Lester GD, Krockenberger MB.Cryptococcus is the most common fungal respiratory pathogen in Australian horses, manifesting primarily as pulmonary granulomas. Disease severity at presentation is dependent on the athletic use of the horse. The diagnosis and estimation of disease severity are centred around clinical findings, cytological evaluation of respiratory tract secretions, diagnostic imaging, and antigen titre testing. Both the lateral flow assay and the latex cryptococcal antigen titre are used, and important similarities and differences between species are discussed. Cryptococcus gattii occurs with greater frequenc...
Wilson RC, Moore JN, Eakle N.The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given end...
Matthews NS, Peck KE, Mealey KL, Taylor TS, Ray AC.Five donkeys and three horses were given guaifenesin, intravenously, by gravity administration, until recumbency was produced. The time and dose required to produce recumbency, recovery time to sternal and standing were recorded. Blood samples were collected for guaifenesin assay at 10, 20, 30, 40, 50, 60 min, and 2, 3, 4 and 6 h after guaifenesin administration. Serum was analysed for guaifenesin using HPLC and pharmacokinetic values were calculated using a computer software package (RSTRIP). In donkeys, heart and respiratory rates and blood pressures were recorded before and at 5-min interva...
