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.
Chapman DI, Marcroft J.1. The metabolism of (±)-[14C]noradrenaline in horses has been studied. The plasma half-life of radioactivity following intravenous injection was 95 min.
2. Two horses each excreted about 80–85% of the radioactivity in the urine in 15 h after rapid intravenous injection and about 75% of the excreted radioactivity has been identified.
3. The unchanged drug in the urine accounted for less than 1% of the dose and 3-methoxynoradrenaline for about 7%. The main metabolites were 4-hydroxy-3-methoxymandelic acid (22%), 4-hydroxy-3-methoxybenzoic acid (13%) and 4-hydroxy-3-methoxyphenylglycol ...
Harkins JD, Tobin T.Fentanyl and other opioid drugs have their effect in the central nervous system; however, activity at peripheral sites has also been demonstrated. Pain-suppression activity at peripheral sites raises the possibility of skilled individuals producing local anaesthetic effects with small doses of opioid drugs that would be difficult to detect forensically and could be used to affect the outcome of a race. Therefore, the local pain-suppression effect (peripheral nerve inhibition) of fentanyl was tested using an abaxial sesamoid block/hoof withdrawal model. With this model, fentanyl did not produce...
Lees P, Taylor JB, Higgins AJ, Sedgwick AD.In vitro and in vivo studies of phenylbutazone binding to equine ingesta and digesta were undertaken. In vitro binding to chopped hay and powdered pony nuts in buffer solutions at 37 degrees C was found to be time-, concentration- and pH-dependent. Percentage binding generally increased with time, decreased with concentration and varied with buffer pH in an unpredictable manner. Other non-steroidal anti-inflammatory drugs (NSAIDs) also bound to hay, the degree of binding being less for meclofenamate and least for flunixin in comparison with phenylbutazone. Phenylbutazone became bound to digest...
Thomasy SM, Slovis N, Maxwell LK, Kollias-Baker C.This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum f...
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...
McElligott EM, Sommardahl CS, Cox SK.OBJECTIVE To determine the pharmacokinetics of chloramphenicol base after PO administration at a dose of SO mg/kg (22.7 mg/lb) in adult horses from which food was not withheld. DESIGN Prospective crossover study. ANIMALS 5 adult mares. PROCEDURES Chloramphenicol base (SO mg/kg) was administered PO to each horse, and blood samples were collected prior to administration (0 minutes) and at 5, 10, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours thereafter. Following a washout period, chloramphenicol sodium succinate (25 mg/kg [11.4 mg/lb]) was administered IV to each horse, and blood samples were ...
Young DB, Ewing PJ, Burrows GE, Lessley BA, Clarke CR, Shawley RV.Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 8.8 mg/kg i.v. phenylbutazone; and 1...
Knych HK, Stanley SD, McKemie DS, Steinmetz SJ.Romifidine is an alpha-2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low-dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography-tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhyt...
Kristinsson J, Thordarson TH, Johannesson T.The pharmacokinetics of lignocaine was studied in four Icelandic horses after infiltration anaesthesia. A total of 240 mg of the drug was injected on either side of the left foreleg, over the medial and lateral branches of the palmar nerve. Blood samples were collected up to seven hours after injection and the concentrations of the drug in plasma were determined by gas chromatography/mass spectrometry. The results showed that lignocaine was rapidly absorbed. A mean maximum concentration of 232 ng/ml was observed after 20 minutes. In three of the horses the decline in the plasma concentration o...
Monclin SJ, Farnir F, Grauwels M.Tetracaine hydrochloride (THCl) has been reported to cause irritation in dogs. In man, some topical anaesthetics have been shown to disrupt the tear film. Tear break-up time (TBUT) is a useful test allowing an assessment of the quality of the precorneal tear film. Only one TBUT value has been reported in horses with no information on the technique used. Objective: To provide a method for performing the TBUT in horses and to report any side effects of a single application of THCl in clinically normal horses, particularly on the stability of the tear film. Methods: In Study 1, one drop of 0.5 or...
Brown MP, Gronwall RR, Houston AE.Four healthy adult mares were each given a single injection of sodium cefoxitin (20 mg/kg of body weight, IV), and serum cefoxitin concentrations were measured serially during a 6-hour period. The mean elimination rate constant was 1.08/hour and the elimination half-life was 0.82 hour. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.12 L/kg and 259 ml/hr/kg, respectively. Each mare and 2 additional mares were then given 4 consecutive IM injections of sodium cefoxitin (400 mg/ml) at a dosage of 20 mg/kg. Cefoxitin concentrations in serum, ...
Huxford KE, Dart AJ, Perkins NR, Bell R, Jeffcott LB.AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments....
Gilger BC, Salmon JH, Wilkie DA, Cruysberg LP, Kim J, Hayat M, Kim H, Kim S, Yuan P, Lee SS, Harrington SM, Murray PR, Edelhauser HF, Csaky KG....To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. Methods: A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep sclera...
Rumpler MJ, Sams RA, Colahan P.We describe a validated, rapid, sensitive, and specific UHPLC-MS/MS method to detect and quantify glycopyrrolate in 0.5 mL of horse urine. Further, we investigated the elimination of glycopyrrolate in urine after both intravenous and oral administration of clinically relevant doses to Thoroughbred horses. Quantification was performed by weighted, linear regression analysis using a deuterated analogue of glycopyrrolate as internal standard (IS). The method was characterized by a linear range of 5-2500 pg/mL, a lower limit of quantification of 5 pg/mL and a limit of detection of 1 pg/mL. The int...
Abutarbush SM, Alfaqeeh SM, Mustafa G, Qura'n L, Al-Majali AM.To evaluate the ability of atropine sulfate, butylscopolammonium bromide combined with metamizole sodium, and flunixin meglumine to ameliorate the clinical adverse effects of imidocarb dipropionate in horses. Methods: 28 horses with piroplasmosis. Methods: 28 horses were randomly assigned to 4 equal groups according to the pretreatment administered. Fifteen minutes before administration of 2.4 mg of imidocarb dipropionate/kg IM, horses in the first group were pretreated with 0.02 mg of atropine sulfate/kg IV, the second group with a combination of 0.2 mg of butylscopolammonium bromide/kg IV an...
Di Salvo A, Giorgi M, Nannarone S, Lee HK, Corsalini J, Della Rocca G.NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 2...
Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S.The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys ( = 5), aged 6-12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume ...
Trevisiol S, Moulard Y, Kaabia Z, Delcourt V, Loup B, Garcia P, Boyer S, Dauriac K, Groseille G, Rouger S, Narbe R, Popot MA, Bailly-Chouriberry L.Ciclesonide (CIC) is the first inhaled highly potent corticosteroid that does not cause any cortisol suppression. It has been developed for the treatment of asthma in human and more recently in equine. CIC is the active compound of Aservo® EquiHaler® (Boehringer Ingelheim Vetmedica GmbH), the pre-filled inhaler generating a medicated mist based on Soft Mist™ technology. This prodrug is rapidly converted to desisobutyryl-ciclesonide (des-CIC), the main pharmacologically active compound. Due to its anti-inflammatory properties, CIC is prohibited for use in horse competitions. To set up an ap...
Lees P, Landoni MF, Giraudel J, Toutain PL.This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administ...
McKibbin LS, Cheng RS.This study showed that subcutaneous injection of a solution of D-amino acids produced effective analgesia in horses. It is postulated that systemic D-phenylalanine and D-leucine may become one of the safe, effective and nonaddictive drugs for acute and chronic pain treatment. These D-amino acids cause analgesia by presumably preserving brain endorphins. They may bind reversibly to enkephalinases and prevent enzymatic degradation of enkephalins.
Gallicano KD, Park HC, Young LM.A sensitive method was required to analyze low levels of camphor in equine urine and plasma. Camphorated oil (20% w/w camphor) was administered topically (6 g) and intratracheally (1 g) to standardbred mares. The drug was extracted from urine and plasma by diethyl ether and analyzed as its 2,4-dinitrophenylhydrazone derivative by reverse phase HPLC with UV detection. The UV detector was set at 368.5 nm and the samples were eluted from the C18 column by 82% acetonitrile in water. The detection limit achieved was about 10 ng/mL urine and about 20 ng/mL plasma. After topical administration, only ...
Auer U, Uray C, Mosing M.To investigate the onset and duration of neuromuscular blockade of rocuronium bromide and its associated haemodynamic effects at three doses in healthy horses. Methods: Prospective, randomized experimental study. Methods: Seven adult horses aged 3-20 (mean 10.3) years and weighing 466 +/- 44 (mean +/- SD) kg. Methods: Horses were anaesthetized three times with at least 2 weeks between. They were pre-medicated with 0.6 mg kg(-1) xylazine and 0.01 mg kg(-1) butorphanol i.v.. Anaesthesia was induced with 2.2 mg kg(-1) ketamine and 0.1 mg kg(-1) diazepam i.v.. Following orotracheal intubation anae...
Weidolf LO, Chichila TM, Henion JD.Methods for screening by thin-layer chromatography, quantification by high-performance liquid chromatography with ultraviolet detection and confirmation by gas chromatography-mass spectrometry of boldenone sulfate in equine urine after administration of boldenone undecylenate (Equipoise) are presented. Sample work-up was done with C18 liquid-solid extraction followed by solvolytic cleavage of the sulfate ester. Confirmatory evidence of boldenone sulfate in equine urine was obtained from 2 h to 42 days following a therapeutic intramuscular dose of Equipoise. The use of 19-nortestosterone sulfat...
Arnoczky SP, Lavagnino M, Gardner KL, Tian T, Vaupel ZM, Stick JA.To determine the effects of oxytetracycline on matrix metalloproteinase-1 (MMP-1) mRNA expression and collagen gel contraction by equine myofibroblasts in an effort to explain the mechanistic basis for the pharmacologic treatment of flexural deformities in foals. Methods: Cultured myofibroblasts from the accessory ligament (distal check ligament) of 6 foals. Methods: Collagen gel scaffolds seeded with equine myofibroblasts were cultured in individual culture dishes containing complete media (Dulbecco's modified Eagle medium with 10% fetal bovine serum) and oxytetracycline (0, 12.5, 25, or 75 m...
Kusano K, Nomura M, Toju K, Ishikawa Y, Minamijima Y, Yamashita S, Nagata S.Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, ...
Hubbell JA, Kelly EM, Aarnes TK, Bednarski RM, Lerche P, Liu Z, Lakritz J.Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. Objective: To determine the pharmacokinetics and sedative effects of midazolam in horses. Methods: Blinded, randomised, crossover design. Methods: Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectromet...
White DA, Hildebrand SV, Jones JH, Fung DL, Gronert GA.On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the ...
Goodrich LR, Furr MO, Robertson JL, Warnick LD.A double-blind study was performed, in horses, to determine the potential toxic effects of the nonsteroidal anti-inflammatory drug, eltenac(4-[(2,6-dichlorophenyl) amino]-3-thiopheneacetic acid). Four treatment groups of six horses were formed. The drug was injected intravenously, once daily, at a dose level of 0.5 mg/kg, 1.5 mg/kg or 2.5 mg/kg for 15 days. A control group was injected with sterile saline solution. Horses were monitored for changes in appetite, physical examinations, biochemical evaluations and gastroscopic examinations. Complete post-mortem examinations were also performed. A...
Carlson A, Johnson PJ, Lei Z, Keegan KG.Soluble epoxide hydrolase (sEH) inhibitors are novel anti-inflammatory and analgesic agents that could improve pain management in horses. The objective of the present study was to evaluate the anti-nociceptive effect of a single-dose intravenous administration of the sEH inhibitor trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB) using an adjustable heart bar shoe (a-HBS) model of lameness. We hypothesized that t-TUCB would improve objective and subjective lameness measures compared to the control. Methods: Reversible lameness was induced in 8 horses for 24...
Igwe OJ, Blake JW.An analytical gas/liquid chromatographic (GLC) protocol is described for the quantitation of pemoline in biological fluids of the horse. Plasma samples containing known quantities of pemoline and its analog as an internal standard (IS) were deproteinized with 5-sulfosalicylic acid, heated at 80 degree C, and centrifuged. 5-Phenyl-2,4-oxazolidinedione, the hydrolytic product of pemoline in acid medium, was extracted with dichloromethane (DCM). The organic layer was in turn re-extracted with 1% NaHCO3. The aqueous layer was acidified with HCI, and re-extracted with DCM, which was evaporated to d...
