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.
BRAYE ET, HINSMAN EJ, RILEY WF.No horse receiving combined streptokinase, streptodornase, and human plasminogen alone in either 125,000-unit or 375,000-unit doses manifested any clinical reaction. Untoward reactions occurred in 2 horses receiving both the combined streptokinase, streptodornase, and human plasminogen (125,000 units), and chlortetracycline. The reaction was transitory and subsided without treatment.
Gough MR, Munroe GA, Mayhew G.This paper tests the hypothesis that the local analgesic agent mepivacaine diffuses between adjacent equine synovial structures in the hindlimb and with greater frequency than latex, gelatine dye or contrast media. We report the incidence of diffusion of mepivacaine between the tarsometatarsal, centrodistal and tarsocrural joints, and the 3 synovial compartments of the stifle in 33 fresh equine cadavers. The tarsometatarsal joint and one synovial compartment of the stifle in the left limb and the centrodistal joint and a different synovial compartment of the stifle in the right limbs were inje...
Pyörälä S, Taponen J, Katila T.Use of antimicrobials for veterinary indications related to reproduction in cattle and horses is reviewed. Antimicrobial compounds are widely used to treat and prevent infections of reproductive organs. Total amounts of antimicrobials for such purposes, estimated by weight, are low compared with major uses in food animals. The most common reproduction-related indication in cattle is mastitis. The number of intramammary products available for treatment of mastitis in the European Union is high. Metritis and endometritis also require antimicrobial treatment of cattle and specific products for in...
Rendle DI, Hughes KJ, Doran GS, Edwards SH.To determine the pharmacokinetics of pergolide after IV administration to horses. Methods: 8 healthy adult horses. Methods: Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. Results: After IV administration of pergolide, mean ± SD clearance, elimination half-life, a...
Sanford J.The usefulness of an antibiotic depends not only upon its antibacterial potency and spectrum but also on the prevalence of resistant organisms and the extent and severity of the adverse reactions to which it may give rise. Variations in formulation of the same compound are reflected in differences in bioavailability. These may be intentional, as in the development of long-acting preparations, but may also be unexpected following differences in drug purity, content and gastro-intestinal absorption. Individual and species differences in treated animals also result in variations in bioavailabilit...
Jonckheere JA, Thienpont LM, De Leenheer AP, De Backer P, Debackere M, Belpaire FM.A method has been developed for quantification of bromhexine in plasma using gas chromatography mass spectrometry with selected ion monitoring. A deuterium labelled analogue was synthesized and used as the internal standard. To evaluate the gas chromatographic electron capture detection method described earlier, 23 plasma samples have been analysed by both techniques. Although a good correlation was shown, selected ion monitoring was superior to the electron capture detection method for levels below 3 ng ml-1. The mass spectrometric method has also been used to set up a pharmacokinetic study o...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Raidal SL, Andrews FM, Nielsen SG, Trope G.Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. Objective: To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Methods: Masked 2 period, 2 treatment crossover. Methods: Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day...
Komáromy AM, Andrew SE, Sapp HL, Brooks DE, Dawson WW.The goal of our study was the evaluation of a practical method for the recording of flash electroretinograms (ERGs) in sedated, standing horses with the DTL microfiber electrode. Methods: The horses were sedated intravenously with detomidine hydrochloride (0.015 mg/kg). The pupil was dilated and the auriculopalpebral nerve was blocked. The ERGs were recorded with the active electrode on the cornea (DTL), the reference electrode near the lateral canthus, and the ground electrode over the occipital bone. The light intensities of the white strobe light were 0.03 cd x s/m2 (scotopic) and 3 cd x s/...
Knych HK, Mama K, Oakleaf M, Harrison LM, McKemie DS, Kass PH.The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
Ensink JM, Klein WR, Barneveld A, Vulto AG, Van Miert AS, Tukker JJ.The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. ...
Echeverria KO, Lascola KM, Giguère S, Foreman JH, Austin SA.OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration. ANIMALS 7 healthy adult horses. PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL ...
McKinney AR, Suann CJ, Stenhouse AM.An investigation was conducted into the stereochemistry of the equine urinary metabolites of 17alpha-methyltestosterone observed after oral administration. Standards of the complete range of C3/C5/C16 stereoisomeric 17alpha-methylandrostane-3,17beta-diols, 17alpha-methylandrostane-3,16,17beta-triols and 17alpha-hydroxymethylandrostane-3,17beta-diols were purchased or synthesised, and were used to unequivocally identify the absolute structures of the metabolites. Phase I metabolism was found to involve combinations of Delta(4)-3-ketone reduction with both 5alpha,3beta- and 5beta,3alpha-stereoch...
Fleitman J, Neu D, Benjamin E.A reverse phase liquid chromatographic procedure is described for the simultaneous determination of oxfendazole [2-(methoxycarbonylamino)-5-phenylsulfinylbenzimidazole] and trichlorfon [(2,2,2-trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester] in equine paste. The sample is extracted by sonication in methanol. Insoluble excipients are removed by centrifugation and an aliquot plus internal standard are diluted with dilution solvent (water-acetonitrile-phosphoric acid, 80 + 20 + 1). The samples are filtered and injected onto a Partisil-5 ODS-3 column with acetonitrile-0.01 M phosphate buff...
Estrada RJ, Alvarado GJ, Vargas A, Vargas J, Vargas D, Chacón R, Razquin P, Vindas R.To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. Methods: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. Methods: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block ...
Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W.Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in h...
Drudge JH, Lyons ET, Tolliver SC.Critical tests were carried out in 10 horses to evaluate the antiparasitic activity of febantel given alone or with trichlorfon. Paste formulations were administered intraorally at dose levels of 6 mg of febantel (active ingredient)/kg and 35 mg of trichlorfon (active ingredient)/kg. In 5 tests with febantel alone, removal of 100% was recorded for mature or immature Parascaris equorum from 2 infected horses. Strongylus vulgaris from 4 infected horses, S edentatus from 5 infected horses, and mature Oxyuris equi from 1 infected horse; and removal of 96% was recorded for small strogyles from 1 ho...
Delatour P, Benoit E, Bourdin M, Gobron M, Moysan F.After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant ...
Decloedt A, Broux B, De Clercq D, Deprez P, Van Steenkiste G, Vera L, Ven S, van Loon G.Based on its pharmacokinetic profile and electrophysiological effects in healthy horses, sotalol potentially could be used as a long-term PO antiarrhythmic drug in horses. Objective: To evaluate the effect of sotalol on heart rate (HR), QT interval, atrial fibrillatory rate, and success of cardioversion in horses with naturally occurring chronic atrial fibrillation (AF). Methods: Twenty-eight horses referred for transvenous electrical cardioversion of AF were treated with 2 mg/kg sotalol PO q12h for 3 days before cardioversion, and 13 horses underwent the same protocol without sotalol administ...
Lescun TB, Ward MP, Adams SB.To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. Methods: 18 horses with clinically normal tarsocrural joints. Methods: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentami...
Peck KE, Ray AC, Manuel G, Rao MM, Foos J.To develop a sensitive, rugged high-performance liquid chromatography (HPLC) method for the measurement of phenylbutazone (PBZ) in equine sera, using a rapid, nonevaporative extraction technique. Methods: Sera from 5 nonexercising adult horses. Methods: After addition of sodium chloride and acetonitrile to serum samples, reverse-phase HPLC analysis for PBZ and oxyphenbutazone (OXY) was performed directly on extracts, using diode array UV spectrophotometric detection. Probenecid was used as an internal standard. Data were evaluated by standard means of statistical analysis. Results: Recoveries ...
Dyke TM, Sams RA.The objective of this study was to determine the urinary excretion of methylxanthines in horses following ingestion of chocolate over eight days. The study was performed in response to gas chromatography-mass spectrometry (GC-MS) confirmation of the presence of caffeine in a positive urine test in a racehorse. The trainer of the horse alleged that he often administered chocolate-coated peanuts as treats to his horses, and he believed that the ingestion of chocolate was responsible for the positive urine test. The urinary excretion of theobromine and caffeine after the ingestion of chocolate-co...
McDonnell SM.This study is part of ongoing work toward developing pharmacological methods for enhancing and inducing ejaculation in stallions with ejaculatory dysfunction or disabilities that interfere with normal breeding behavior. The objective was to evaluate a treatment regimen involving oral imipramine followed by intravenous xylazine that, in uncontrolled field clinical trials, had shown promise for a higher rate of ejaculation and fewer side effects using a more easily obtained and administered form of imipramine. Eight stallions each underwent eight trials in which treatment consisted of imipramine...
Choi TLS, Wong JKY, Kwok WH, Curl P, Mechie S, Wan TSM.Methylstenbolone (2,17α-dimethyl-5α-androst-1-en-17β-ol-3-one) is a synthetic anabolic and androgenic steroid (AAS) sold as an oral 'nutritional supplement' under the brand names 'Ultradrol', 'M-Sten' and 'Methyl-Sten'. Like other AASs, methylstenbolone is a prohibited substance in both human and equine sports. This paper describes the studies of the in vitro and in vivo metabolism of methylstenbolone in horses using LC/HRMS, GC/MS and GC/MS/MS. Phase I in vitro metabolic study of methylstenbolone was performed using homogenised horse liver. Hydroxylation was the only biotransformation obse...
Viljanto M, Kaabia Z, Taylor P, Hincks P, Muir T, Habershon-Butcher J, Bailly-Chouriberry L, Scarth J.Boldenone is an anabolic-androgenic steroid (AAS) that is prohibited in equine sports. However, in certain situations, it is endogenous, potentially formed by the microbes in urine. An approach to the differentiation based on the detection of the biomarkers Δ1-progesterone, 20(S)-hydroxy-Δ1-progesterone and 20(S)-hydroxyprogesterone was assessed, and their concentrations were monitored in the urine of untreated female horses (n = 291) alongside boldenone, boldienone, testosterone and androstenedione. Using an ultra-sensitive analytical method, boldenone (256 ± 236 pg/mL, n = 2...
Dimaio Knych HK, Steffey EP, Stanley SD.Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered a...
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 ...
Authie EC, Garcia P, Popot MA, Toutain PL, Doucet M.Equine antidoping rules were established to prevent a horse's performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Veterinarians have to advise owners or trainers on appropriate withholding times to guarantee that their horses may safely compete after drug administration. In order to propose tailored withdrawal times, several horse organisations released detection time (DT) values, for the main veterinary drugs used in horses. One of the possible limits to the information provided by published DTs in horses is the ...
Jackman BR, Moore JN, Barton MH, Morris DD.The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiatin...
Armstrong S, Tricklebank P, Lake A, Frean S, Lees P.Carprofen is a Non Steroidal Anti-Inflammatory Drug (NSAID) which is widely used for the treatment of musculoskeletal disorders in horses. The commercial preparation is a racemic mixture of two enantiomers (R and S carprofen). We used HPLC to measure plasma and synovial fluid R and S carprofen concentrations following a single intravenous (i.v.) dose, and computer modelling to determine the pharmacokinetic parameters of the enantiomers in these two body fluids. A comparison was made with results from an identical experiment using ketoprofen. The plasma elimination half lives of R and S carprof...
O'Brien M, Mochel JP, Kersh K, Wang C, Troy J.Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics ...
