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.
Lees P, Higgins AJ.A model of acute inflammation was used in a cross-over study in Welsh mountain ponies to assess the actions of flunixin meglumine on selected components of a localised inflammatory reaction induced by injecting 0.5 ml of a 2 per cent carrageenin solution into subcutaneously implanted tissue cages. Samples of exudate were harvested at predetermined times between three and 48 hours. Increases in leucocyte numbers and protein concentration were not prevented by flunixin treatment. Prostaglandin E2-like activity was present in exudates from untreated ponies with the highest mean concentration occu...
Yang JM, Woods WE, Weckman TJ, Wood TW, Chang SL, Blake JW, Tobin T.1. Drug administration studies using diisopropylamine dichloroacetate (DADA) and diisopropylamine (DIPA) were conducted in Thoroughbred and Standardbred horses to assess physiological effects and develop detection methods. 2. Four horses received 0.08 mg DADA/kg body wt and showed no changes in heart and respiratory rates or body temperature as measured over a 1-hr period after administration. A transient diuretic effect was found to occur in 2 mares dosed with 0.80 mg DADA/kg body wt. 3. A qualitative detection method using thin-layer chromatography was developed to detect DIPA, the major met...
Aguilera-Tejero E, Pascoe JR, Smith BL, Woliner MJ.To investigate the influence of increased respiratory frequency on respiratory mechanics in the horse, measurements were made in two groups of seven tracheostomized horses before and after the administration of doxapram. The horses in group I had normal base line values for respiratory mechanics, whereas the horses in group II had significantly lower values of dynamic compliance (Cdyn), higher respiratory resistance (R), and a higher total change in pleural pressure (delta P). The administration of 0.3 mg kg-1 doxapram intravenously resulted in a significant increase in respiratory frequency (...
Hamamoto-Hardman BD, Steffey EP, Seminoff K, McKemie DS, Kass P, Knych HK.Although morphine has demonstrated antinociceptive effects in horses, its administration has been associated with dose-dependent adverse effects. In humans and rats, part of the analgesic effect of morphine has been attributed to the active metabolite, morphine-6-glucuronide (M6G). Although morphine can cause several undesirable effects, M6G has a more favorable safety profile. The objective of this study was to characterize the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of M6G following intravenous administration to a small group of horses. In Part ...
Toutain PL, Autefage A, Legrand C, Alvinerie M.The purpose of the present study was to establish in the horse the relationship between plasma concentration profiles of phenylbutazone (PBZ) and flunixin meglumine (FM) and their pharmacological effects in order to build a predictive pharmacokinetic/pharmacodynamic (PK/PD) model. In five horses, an experimental arthritis was induced by injecting Freund's adjuvant into a carpal joint. PBZ (4 mg/kg) and FM (1 mg/kg) were injected by the intravenous route as a single intravenous dose in two different trials. Five pharmacodynamic end-points were regularly measured after test article injection usi...
Goetz TE, Munsiff IJ, McKiernan BC.The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.0...
Riddolls LJ, Byford GG, McKee SL.The biological and imaging characteristics of technetium-99m imidodiphosphate (Tc99m-IDP) were measured in 4 horses once and in 1 horse twice. All computational results are expressed with 95.5% (mean +/- 2 SD) confidence limits. The clearance half-time of the radiopharmaceutical from the blood was 29.6 +/- 2.3 min. The percentage of the administered dose circulating in the whole-blood volume at 4 h was 3.9 +/- 0.8%. The Tc99m-IDP radioactivity confined at the plasma fraction of the whole blood at 4 h was 85.3 +/- 1.6%. At 8 h, approximately 45 +/- 16% of the dose administered had been excreted...
Martins FC, Keating SC, Clark-Price SC, Schaeffer DJ, Lascola KM, DiMaio Knych H.To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Martinez PS, Whitley RD, Plummer CE, Richardson RL, Hamor RE, Wellehan JFX.To examine the relationship between Minimum Inhibitory Concentration (MICs) and response to therapy of 6 Fusarium spp. and 5 Aspergillus fumigatus isolated from equine ulcerative keratitis cases. Methods: Fungi were identified by morphology and Internal Transcribed Spacer (ITS) polymerase chain reaction (PCR) with sequencing and evaluated at the University of Texas Fungal Testing Laboratory for susceptibility to three azole antifungals (miconazole, voriconazole, posaconazole), natamycin, and two echinocandins (anidulafungin, caspofungin). A Mann-Whitney rank sum test was used for the compariso...
Boyce M, Malone ED, Anderson LB, Park S, Godden SM, Jenner F, Trumble TN.To determine whether triamcinolone acetonide diffuses from the distal interphalangeal joint (DIPJ) to the navicular bursa, diffusion is direct or systemic, and addition of sodium hyaluronan has an effect on diffusion in horses. Methods: 11 adult horses without forelimb lameness. Methods: 1 randomly chosen forelimb DIPJ of each horse received an injection of 10 mg of triamcinolone acetonide plus 20 mg of sodium hyaluronan (group 1), and the contralateral forelimb DIPJ received an injection of 10 mg of triamcinolone acetonide plus 2 mL of lactated Ringer's solution (group 2). Synovial fluid samp...
Lyons ET, Tolliver SC, Drudge JH, Swerczek TW.Oxfendazole paste formulation was administered intraorally at a dosage of 10 mg/kg of body weight, twice (48 hours between treatments) in 5 controlled tests (experiments A, B, C, D, and E) to 18 equids (14 horses and 4 ponies) that were 5 to 24 months old in 1986 and 1987. Activity was evaluated against naturally acquired infections of various internal parasites, with emphasis on migratory stages of Strongylus vulgaris and S edentatus. The number of treated and nontreated equids in each experiment (horses in experiments A to D and ponies in experiment E) was: A, 1 and 1; B, 3 and 3; C, 3 and 1...
el-Banna HA.The pharmacokinetic aspects of sulphadimidine were studied in clinically healthy (control) and Flunixin-medicated horses after a single intravenous and oral administration of 100 mg/kg body weight. Plasma sulphadimidine concentration were determined by high-performance liquid chromatography (HPLC). Following the intravenous injection, all plasma sulphadimidine data were best approximated by a two-compartment open model using sequential, weight non-linear regression. Flunixin induced a 67% increase in the rate of sulphadimidine return to the central compartment from peripheral tissues (K21) and...
Harvey A, Kilcoyne I, Byrne BA, Nieto J.To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. Methods: Randomized crossover experiment. Methods: Six adult horses. Methods: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints...
Duvivier DH, Chiap P, Crommen J, Lekeux P.The aim of this study was to determine the effect of breathing pattern, air humidity and position of the device on the delivery of an aerosol generated by a dry powder inhalation (DPI) device (Inhalator M). The in vitro inhalation study was performed using the cascade impaction method (Andersen Sampler) adapted to imitate nasal breathing. The amount of ipratropium found in the device, the artificial upper airways and the six stages of the Andersen Sampler was measured using high precision liquid chromatography. Stage 1 of the Andersen Sampler was considered to be the respirable fraction and st...
Fey K, Klatt P, Schmidt H, Sasse HH.Five healthy horses were given a sulfadoxine/trimethoprim combination (Borgal, Hoechst AG) i.v. on day 1. The next ten days the horses got once a day a sulfadimethoxine/trimethoprim combination orally (Trafigal, Hoechst AG). The doses were given as recommended. One horse received no medicaments for control. On each horse six bronchoalveolar lavages were performed. Blood samples were taken to calculate blood levels and elimination half lives. To determine the amount of substances in lavage fluid and plasma the high performance liquid chromatography (HPLC) was used. Regularly low quantities of s...
Presson BL, Hamm D, Yazwinski TA, Pote LM.Critical tests were performed on 6 horses to evaluate the antiparasitic effectiveness of oxfendazole given in combination with trichlorfon in a paste formulation. Treatments were given orally as a single dose. The rates of active ingredient administration were 2.5 and 40 mg/kg of body weight for oxfendazole and trichlorfon, respectively. The combined activities of the 2 antiparasitic compounds proved 100% efficacious in the removal of adult Strongylus vulgaris, S edentatus, Oxyuris equi, and Parascaris equorum. Fourth stage O equi, and 2nd and 3rd instars of Gasterophilus nasalis also were com...
Schwarzwald CC, Sams RA, Bonagura JD.The pharmacokinetics of diltiazem were determined in eight healthy horses. Diltiazem HCl, 1 mg/kg i.v., was administered over 5 min. Venous blood samples were collected at regular intervals after administration. Plasma concentrations of diltiazem and desacetyldiltiazem were determined by high-performance liquid chromatography. A second, putative metabolite was detected, but could not be identified due to the lack of an authentic standard. Data were analyzed by nonlinear least-squares regression analysis. The median (minimum-maximum) peak plasma concentration of diltiazem was 727 (539-976) ng/m...
Mahne AT, Rioja E, Marais HJ, Villarino NF, Rubio-Martinez LM.Antimicrobial i.v. regional limb perfusion (IV-RLP) is clinically performed on anaesthetised or sedated horses with or without regional anaesthesia. To date, no scientific data are available on the clinical and pharmacokinetic effects of these anaesthetic protocols on antimicrobial IV-RLP, which is believed to result in better tourniquet efficiency due to decreased movement. Objective: To determine the effects of regional or general anaesthesia on the clinical and synovial pharmacokinetic parameters of amikacin administered by IV-RLP to horses. Methods: Experimental crossover study. Methods: E...
Horspool LJ, McKellar QA.The present study was designed to determine and compare the plasma disposition and pharmacokinetics of penicillin G sodium following intravenous (i.v.) administration to horses, ponies and donkeys. The plasma disposition and pharmacokinetics of penicillin G was similar in horses, ponies and donkeys (elimination half-lives--39.0, 27.3 and 31.5 min, respectively) and a dosage interval of 6-8 h would be suitable to treat infections caused by susceptible bacteria. Although penicillin G was absorbed rapidly following nasogastric administration, the systemic availability was low (0.12-0.34%), theref...
Reed RA, Knych HK, Barletta M, Sakai DM, Ruch MM, Smyth CA, Ryan CA.To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. Methods: Randomized, masked, crossover design. Methods: A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. Methods: Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for ...
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...
