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.
Sams R, Gerken DF, Ashcraft SM.The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high-performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half-life of ketoprofen after th...
Lavy E, Ziv G, Glickman A.An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus asinus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45-60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2 beta) was 209 +/- 36 min, the apparent vol...
Soraci A, Benoit E, Jaussaud P, Lees P, Delatour P.Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours afte...
Mama KR, Steffey EP, Pascoe PJ.This study provides baseline information on the potential use of propofol as a general anesthetic for horses. Using a Latin square design, propofol (2, 4, and 8 mg/kg) was administered intravenously on three separate occasions to six mature horses. Information about anesthetic induction, duration, and recovery was recorded along with results of rectal temperature, heart rate, respiratory rate, pHa, PaCO2 and PaO2. Statistical analysis included a mixed model analysis of variance, a general linear model analysis and least square means test for post hoc comparisons. A P < .05 was considered si...
Breukink HJ, Eysker M.Now and then cases have been reported where horses died suddenly after intravenous application of Ivomec. Lethal anaphylactic reactions in horses are known to occur incidentially after intravenous application of drug dissolved in propyleneglycol or glycerolformol. Since Ivomec is registered for use in cattle, sheep and pig, its use in horses has to be regarded as 'off label use'. It is concluded that in the treatment of inhibited stages of cyathostomes ivermectin has no effect whether or not it is applied intravenously or orally. Since lethal anaphylactic reactions can occur, intravenous appli...
van Duijkeren E, Vulto AG, Sloet van Oldruitenborgh-Oosterbaan MM, Kessels BG, van Miert AS, Breukink HJ.In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bi...
Monahan CM, Chapman MR, French DD, Klei TR.During a series of dose-titration experiments designed to evaluate the efficacy of moxidectin oral gel against equine gastrointestinal parasites, infection with Onchocerca cervicalis was diagnosed in 25 of 82 ponies prior to treatment. Microfilariae were identified in full-thickness skin biopsies taken from the ventral midline. Treatment with moxidectin in single doses of 300, 400, or 500 micrograms/kg of body weight was 100% effective in eliminating microfilariae from 20 skin biopsies taken 14 days posttreatment, whereas 5 microfilaria-positive ponies in 2 control groups remained positive fol...
Dowling PM, Wilson RC, Tyler JW, Duran SH.The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 157.89 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 +/- 3.99 mL/min/kg. Volume of distribution at stead...
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...
Lyons ET, Tolliver SC, Stamper S, Drudge JH, Granstrom DE, Collins SS.Praziquantel injectable formulation was administered at 0.5 mg k-1 per os to 24 equids naturally infected with 1-183 (average 40) Anoplocephala perfoliata. Drug activity was evaluated by a modified critical test method with necropsy 24 h after treatment. There was variable efficacy of 0-100% (aggregate average 85%); for 18 equids, 93-100%, for three equids, 70-85%, and for three equids, 0-20%.
Chen CL, Goldberg J, Gronwall RR.A radioimmunoassay was developed for prednisolone using IgG purified from rabbit antiserum. The assay was employed to determine the pharmacokinetics of prednisolone following intravenous administration of 450 mg of prednisolone sodium succinate (Solu Delta Cortef) to five adult Thoroughbred horses. The RIA had a sensitivity of 2 ng/ml and was relatively specific. It had cross-reactivity with 21-deoxycortisol (83.3%) cortisol (27.8%), 11-beta-hydroxyprogesterone (39.2%) and 17-hydroxyprogesterone (50%). However, it did not cross-react with naturally occurring steroids (cholesterol, testosterone...
Gronert GA, Fung DL, Jones JH, Shafer SL, Hildebrand SV, Disbrow EA.We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmaco...
Roncada P, Tomasi L, Montesissa C, Grossi G, Stracciari GL, Anfossi P.The kinetics of 2 formulations of theophylline were studied in horses. In an initial cross-over study (Phase I) serum concentration-time curves were determined for granulated and microencapsulated theophylline after a single oral administration (5 mg/kg bwt). In Phase II microencapsulated theophylline was administered at 5 mg/kg bwt/12 h for 10 days at feeding time, as in normal clinical practice. Although no significant differences between the 2 preparations were found with respect to the main kinetic parameters, the microencapsulated form was more evenly and completely absorbed from the dige...
Salvadori MC, Rieser EM, Ribeiro Neto LM, Nascimento ES.The seeds of Guaraná are rich in xanthines and are used for the preparation of guaraná powder which is very commonly given to horses as a 'tonic' in Brazil. In this paper, the xanthine content of guaraná powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guaraná powder was found to contain 2.16, 1.10 and 36.78 mg g-1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in ...
Aida H, Mizuno Y, Hobo S, Yoshida K, Fujinaga T.The minimum alveolar concentration (MAC) of sevoflurane required to prevent gross purposeful movement in response to electrical stimulation of the oral mucous membranes was determined in horses, and their physical responses to inhalation of this anesthetic were observed. The MAC was 2.31 +/- 0.11%. The horses showed good ventilation, without any signs of airway irritation such as coughing. The horses became slightly excited before they laid down. The end tidal sevoflurane concentration (ESC) required to produce recumbency was 2.54 +/- 0.11%. These results suggest that sevoflurane is a clinical...
Schoene C, Nedderman AN, Houghton E.Little is known about the metabolism of 17 alpha-alkyl anabolic steroids in horses. In this study, the metabolism of 17 alpha-methyltestosterone is investigated by oral administration of a (1 + 1) mixture of the steroid and its deuteriated analogue. Both compounds were synthesized from dehydroisoandrosterone (DHA), using a Grignard reaction followed by an Oppenauer oxidation. Post-administration urine extracts were analysed by gas chromatography--mass spectrometry (GC-MS) using both electron impact (IE) and chemical ionization (CI). Interpretation of the data was facilitated by observation of ...
van Duijkeren E, Vulto AG, Sloet van Oldruitenborghoosterbaan MM, Mevius DJ, Kessels BG, Breukink HJ, van Miert AS.The biopharmaceutical properties of four fixed trimethoprim/sulfonamide combinations were investigated in the horse. Eight fasted horses were dosed at 1 week intervals in a sequentially designed study with one intravenous (i.v.) and three oral trimethoprim/sulfadiazine (TMP/SDZ) formulations (1, 2 and 3) administered at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulfadiazine (SDZ). Plasma concentrations of each compound were monitored for 48 h. Pharmacokinetic parameters (volume of distribution, bioavailability and total body clearance) for TMP and SDZ were calculated and compared. Afte...
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...
Kamerling SG, Owens JG.The actions of most drugs are dependent upon achieving adequate plasma concentrations. Plasma concentrations are influenced by the degree to which a drug is absorbed, distributed, metabolized and excreted. Pharmacokinetic assessment reflects changes in these variables as a function of time. Pharmacodynamics refers to specific drug effects or mechanisms of drug action. Individual drug pharmacokinetics provides information on which to base a therapeutic dose, route of administration and dosing interval. However, not all drug actions temporally correlate with plasma kinetics. To resolve this disc...
Delbeke FT, Landuyt J, Debackere M.Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal conc...
Abass BT, Weaver BM, Staddon GE, Waterman AW.The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre-medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three-compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half-life 1.4 +/- 1.2 min (mean +/- SD) and 1.3 +/- 0.7 min, respectively, was obtained, which was followed by a second comparativ...
van Duijkeren E, van Klingeren B, Vulto AG, Sloet van Oldruitenborgh-Oosterbaan MM, Breukink HJ, van Miert AS.The in vitro activity of trimethoprim (TMP) and 9 sulfonamides and their combinations in 6 concentration ratios was tested against 62 Salmonella strains isolated from horses over a 3-year period in the Netherlands, using the agar-dilution method. Most of the isolates were S typhimurium strains (n = 52); the others were S heidelberg (n = 3), S hadar (n = 2), S thompson (n = 2), S enteritidis (n = 1), S infantis (n = 1), and S derby (n = 1). The minimal TMP concentration at which 50% of the Salmonella strains were inhibited (MIC50) was 0.12 micrograms/ml. Sulfachlorpyridazine (SCP; MIC50, 16 mic...
Marroum PJ, Webb AI, Aeschbacher G, Curry SH.A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pat...
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...
Schmid A, Schmid H.In this paper, the metabolism of xenobiotics in the horse, including differences to other species, is discussed. The most important metabolic reactions of phase I (oxidation, reduction and hydrolysis of substrates), as well as of phase II (conjugation of substrates with glucuronic acid, sulphuric acid, acetic acid, alkyl groups, amino acids, amino acid derivatives, glutathione etc.), are discussed and enzymes involved in the metabolic reactions are considered.
Golenz MR, Wilson WD, Carlson GP, Craychee TJ, Mihalyi JE, Knox L.The suitability of the intraosseous (i.o.) route for drug administration to equine neonates was evaluated in a study comparing the pharmacokinetics of amikacin administered by the i.o. and intravenous (i.v.) routes. Using a cross-over study design amikacin sulphate (7 mg/kg bwt) was administered i.o. or i.v. to 6 healthy foals at 3 and 5 days of age. Amikacin was instantaneously and completely absorbed after i.o. administration, achieving a mean +/- sd peak concentration (34.17 +/- 3.54 micrograms/ml) in the first sample collected 3 min after administration which was not significantly differen...
Manohar M.High-intensity exercise results in a dramatic increase in mean pulmonary capillary blood pressure of horses, and administration of furosemide 4 hours before exertion significantly attenuates this exercise-induced increment. To test whether this effect of furosemide is mediated via release of prostaglandins, right atrial and pulmonary vascular pressures were measured in 8 healthy, sound, exercise-trained Thoroughbreds at rest and during incremental-step exercise on a treadmill. Horses were studied on 3 separate occasions: after i.v. administration of saline (0.9% NaCl) solution, after administr...
Bouckaert S, Voorspoels J, Vandenbossche G, Deprez P, Remon JP.Quinidine is the drug of choice for the treatment of cardiac arrhythmias in horses. The plasma concentrations vs. time profiles following oral administration of two formulations of quinidine sulphate, an oral solution and an oral suspension paste, were evaluated in nine horses. They received multiple administrations of the oral solution under fed and non-fed conditions and of the paste under non-fed conditions. A loading dose of 20 mg.kg-1 and a maintenance dose of 10 mg.kg-1 quinidine with dosing interval of 6 h were used. The relative bioavailability of the oral solution under fed conditions...
Wakuno A, Aoki M, Kushiro A, Mae N, Maeda T, Yamazaki Y, Minamijima Y, Nagata SI, Ohta M.To investigate the clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses, seven Thoroughbred horses were randomly anaesthetised twice with either 1 or 2 mg/kg of intravenous alfaxalone after premedication with medetomidine (6 µg/kg intravenous) and midazolam (20 µg/kg intravenous). Blood samples were collected at predetermined time points up to two hours after administration. Plasma alfaxalone concentrations were quantified by a liquid chromatography tandem-mass spectrometry method and analysed by non-compartmental pharmacokinetic analy...
Stein F, Gilliam L, Davis J, Taylor J.In a randomized crossover design study, 10 adult horses were administered crushed metronidazole tablets rectally at 20 mg/kg. Horses' rectums were either evacuated (E) or not evacuated (NE) of manure prior to the administration of the drug. Serum samples were taken over 24 hr and plasma concentrations were determined via high pressure liquid chromatography. At 15 min post-administration, group E had a significantly higher plasma concentration (p = 0.027), but there were no concentration differences at any other time points. There was large variability in relative bioavailability in the NE...
Soma LR, Sams R, Duer W, Tobin T, Woodward C, McDonald J.The plasma and serum concentrations of phenylbutazone (PBZ) and oxyphenbutazone were measured in 158 Thoroughbred horses after various doses of PBZ wer given. All horses were competing or training at racetracks in various parts of the country. All horses used in the study had not been given PBZ 24 hours before they were placed on a specific dosage schedule. Samples were collected 24 hours after the last PBZ administration. Four grams of PBZ were given daily by stomach tube, paste, or tablet for 3 days. On day 4, 24 hours before sample collection, an IV dose of 2 g of PBZ was given, regardless ...
French DD, Klei TR, Taylor HW, Chapman MR, Wright FR.The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective aga...
Hillidge CJ, Lees P.Cardiac output in the horse was measured before and at predetermined times during 2-hour periods of thiopentone-halothane and thiopentone-diethyl ether anaesthesia. Left ventricular stroke volume was decreased to a similar extent during anaesthesia with each volatile agent, but a greater reduction in cardiac output occurred during halothane anaesthesia. This finding reflected the differing effects of halothane and ether on heart rate, a slight bradycardia occurring with the former agent while ether produced a small degree of tachycardia. The latter effect was attributed to enhanced sympathoadr...
Makhaeva GF, Iankovskaia VL, Kovaleva NV, Fetisov VI, Malygin VV, Torgasheva NA, Khaskin BA.The interaction kinetics of potential pesticides, O,O-dialkyl S-bromomethylthiophosphates (RO)2P(O) SCH2Br (R = Et, i-Pr, n-Pr, n-Bu, or n-Am) with acetylcholinesterase, butyryl cholinesterase, and carboxyl esterase from warm-blooded animals was studied. All the compounds irreversibly inhibit these esterases, with k1 (M-1 min-1) being 1.8 x 10(4) - 1.9 x 10(6) for acetylcholinesterase, 2.0 x 10(6) - 4.1 x 10(7) for the more sensitive butyryl cholinesterase, and 2.3 x 10(7) - 2.3 x 10(8) and higher for the most sensitive carboxyl esterase. By using the Hansch and Kubinyi technique of multiple r...
Giorgi M, Mengozzi G, Raffaelli A, Saba A.Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase-5 lipoxygenase). In the horse, it predominantly triggers a strong cyclooxygenase inhibition; this bias seems to be due to the action of its metabolite(s). Among these, only the RWJ-20142 is well known, while to the best of our knowledge no information is available on the other metabolites produced in vivo. Hence, the identification of its main metabolic pathway is pivotal to better understand its clinical activity. A suitable high performance liquid chromatography method has been applied to liquid ...
Eckers C, Skrabalak DS, Henion J.We describe an integrated micro-liquid chromatograph/mass spectrometer (micro-LC/MS) system capable of performing routine determinations for 1--10 ng of drugs and their metabolites extracted from biological fluids. The micro-LC is constructed from conventional "high-performance" liquid-chromatographic instrumentation by using commercially available components. The mass spectrometer is operated in the chemical ionization mode. The direct liquid introduction micro-LC/MS interface can be constructed from commercially available materials. Chromatographic and mass spectral results demonstrate the a...
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...
Du J, Eddington N.A sensitive and selective HPLC method for the determination of the disaccharides of chondroitin sulfate in horse and dog plasma was validated. Chondroitin sulfate is degraded by chondroitinase ABC to three primary unsaturated disaccharides, (1) 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose, (2) 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose, and (3) 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose, when treated with chondroitinase. Plasma samples (0.5 ml) were treated with 50 mU of chon...
Delatour P, Garnier F, Maire R.After administration of the racemic drug, the stereoselective quantification of the enantiomers of free and conjugated carprofen was performed in human plasma and in plasma, urine and bile of dogs and horses. In humans, the plasma profile of free carprofen and its glucuronides is not stereoselective and the glucuronides excreted in urine are close to a racemate. In dogs and horses on the contrary, the R(-) enantiomer of the free drug is predominant in plasma, while urine and/or bile concentrations of the glucuronides are high in comparison to plasma with a strong selectivity for the S(+) enant...
Smith KM, Maxwell L, Gull T, Payton ME, Gilmour MA.To establish the effect of storage in a constant-rate infusion (CRI) pump on the sterility and stability of voriconazole 1% solution. Methods: Nine vials of voriconazole (Vfend(®) I.V.) 1% solution were prepared. Approximately half of each solution was used to prime a commercially available CRI pump with attached subpalpebral lavage system (CRI/SPL unit) with the remaining solution stored in the commercial glass vial. Three CRI/SPL units and their three corresponding vials were stored at one of three temperatures: 23 °C, 33 °C, and 40 °C. The CRI pumps ran for 7 days, and the vials were st...
Knych HK, Steinmetz SJ, McKemie DS.The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospin...
Ayres JW, Pearson EG, Riebold TW, Chang SF.The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 h...
Heffron B, Benoit M, Bishop J, Costello S, Hurt L, Simpson L, Taddei L, Kline K, Negrusz A.During prolonged strenuous exercise, racehorses can experience acidemia. To counteract this phenomenon, trainers can administer blood alkalizing agents that raise the plasma pH and total carbon dioxide (TCO2) concentration. In Illinois, the administrative threshold for TCO2 in plasma is 37.0 mmol/L. Because accuracy in the reported measurement of TCO2 must be ensured, uncertainty measurements are often issued alongside the reported concentrations. We report a validated method for measuring TCO2 levels in equine plasma using the Beckman UniCel DxC 600. A six-point calibration curve ranging from...
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...
Muir WW, Lerche P, Erichson D.Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objective: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1-5 mg/kg bwt) o...
Spallek A, Recknagel S, Breuer J, Koeller G, Schusser GF.The use of laxatives is crucial in the treatment of horses with large colon impaction. To reach the impacted mass, the laxative must leave the stomach and pass through the small intestine. The aim of this study was to determine whether the most frequently used saline and lubricant laxatives influence gastric emptying. Six fasted normal adult Warmblood horses were used in a randomized study design with five laxative trials (1.8% sodium sulfate [1.8% Na2SO4], 4.2% magnesium sulfate [4.2% MgSO4], mineral oil [MOil], 25% sodium sulfate [25% Na2SO4], 25% magnesium sulfate [25% MgSO4]) and two trial...
Minamijima Y, Kuroda T, Kamiya T, Sone Y, Wakuno A, Ito H, Nomura M, Leung GN, Kinoshita K, Yamada M.This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain mo...
Gustafsson K, Sykes BW, Verwilghen D, Palmers K, Sullivan S, van Galen G.Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are re...
Paranjape VV, Knych HK, Berghaus LJ, Cathcart J, Giancola S, Craig H, James C, Saksena S, Reed RA.Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. Unassigned: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h and 40 μg h dosing) in healthy adult horses. Unassigned: Randomised experimental study with a Latin-square design. Unassigned: Six adu...
You Y, Missanelli JR, Proctor RM, Haughan J, Robinson MA.Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Sa...
Zscherpe P, Kalbitz J, Weber LA, Paschke R, Mäder K, von Rechenberg B, Cavalleri JV, Meißner J, Klein K.Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties ag...
Nelson GR, Mama KR, Weiner D, McKemie DS, Kass PH, Steinmetz SJ, Knych HK.This study describes the pharmacokinetics and pharmacodynamics, including antinociceptive effects, of a transdermal buprenorphine solution in horses. It was hypothesized that transdermal application would lead to sustained blood concentrations and antinociceptive effects with fewer adverse effects compared with intravenous (IV) injection. Methods: Prospective nonrandomized four-part parallel experimental study. Methods: A group of eight horses (three mares and five geldings) aged 6-12 years. Methods: Horses were administered incremental doses of 15, 30 and 45 μg kg of buprenorphine transderma...
Wong ASY, Yuen BP, Wong COL, Kong FK, So YM, Kwok WH, Brooks L, Wan TSM, Ho EN.Bisphosphonates and myo-inositol trispyrophosphate (ITPP) are two classes of difficult-to-detect polar drugs that are prohibited under the rules of racing. ITPP is a drug capable of increasing the amount of oxygen in hypoxic tissues, and studies have shown that administration of ITPP increases the maximal exercise capacity in mice. The properties of ITPP make it an ideal candidate as a doping agent to enhance performance in racehorses. In recent years, ITPP had indeed been detected in racehorses and confiscated items. As for bisphosphonates, it is especially critical to control their use as si...
Cutler C, Viljanto M, Hincks P, Habershon-Butcher J, Scarth J, van Eenoo P.S-23 is an arylpropionamide selective androgen receptor modulator that has been investigated in animal models for use as a male hormonal contraceptive but is not yet available therapeutically. S-23 is available alongside other selective androgen receptor modulators (SARMs) to purchase online via uncontrolled sites, sold as supplement products. It has been detected in several human doping cases, highlighting the importance of identifying the best analytical targets for equine doping control. The purpose of this study was to investigate the detection of S-23 and its phase I metabolites in equine...
Michanek P, Bröjer J, Lilliehöök I, Fjordbakk CT, Löwgren M, Hedeland M, Bergquist J, Ekstrand C.Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, ...
Ishii H, Shigematsu R, Takemoto S, Ishikawa Y, Mizobe F, Nomura M, Arima D, Kunii H, Yuasa R, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN.Osilodrostat, used to treat Cushing's disease, exhibits an anabolic effect, leading to its classification as a prohibited substance in horseracing and equestrian sports. This study reports the characterization of osilodrostat metabolites in horse urine and elucidates its metabolic pathways for the first time for doping control purposes. Methods: Osilodrostat was administered nasoesophageally to four thoroughbreds (one gelding and three mares) at a dose of 50 mg each. Potential metabolites were extensively screened via our developed generic approach employing differential analysis to identify m...
Loy J, Cawley A, Sornalingam K, Scrivener CJ, Keledjian J, Noble GK.Altrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determ...
Wong JKY, Choi TLS, Wong COL, Curl P, Wan TSM, Ho ENM.Methylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur-containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti-inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination ...
