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.
Schneider NR, Yeary RA.Elimination kinetics of nitrite and nitrate in the dog, sheep, and pony were determined. The elimination half-lives of nitrite were 0.499, 0.475, and 0.566 hours in the dog, sheep, and pony, respectively; those of nitrate were 44.681, 4.233, and 4.821 hours. Apparent specific volumes of distribution (V'd) of nitrite were variable among the 3 species--1,623.7 ml/kg in the dog, 278.0 ml/kg in the sheep, and 191.6 ml/kg in the pony. The V'd of nitrate were less varied--dog, 238.5 ml/kg; sheep, 291.1 ml/kg; and pony, 209.3 ml/kg. In the in vitro studies on protein binding in canine plasma, the ext...
Nouws JF.As part of the examination of emergency-slaughtered animals for the presence of antibiotic residues, studies were done to see whether false-positive results would be obtained when the Sarcina lutea kidney test and Bacillus subtilis BGA test were performed. When the S. lutea kidney test was positive in cattle, calves and swine, penicillin was invariably found to be present in those animals, the histories of which showed that they had not been given antibiotics. A syringe and an injected fluid containing penicillin residues are regarded as possible causes of these positive results. When the S. l...
Tobin T, Tai CY, Arnett S.A published method for the recovery of procaine from human plasma using 5M NaOH gave very poor recoveries. Investigation showed that under the recommended extraction conditions procaine was rapidly hydrolysed. Extraction into benzene of samples buffered to pH 9.0 with borate buffer allowed essentially 100% recovery of procaine from equine plasma and urine.
Cabler P, Geddes LA, Rosborough J.Ultrasonic energy, provided by a commercially available water vaporizer, was used to vaporize methoxyflurane, halothane, and chloroform. The vaporizer was placed directly in the respiratory line, and the anaesthetic liquid was vaporized one drop at a time. Anaesthesia was maintained for periods up to 6 hr in horses, ponies, calves, sheep, dogs, and one pig. This method of vaporizing liquids is applicable to a wide variety of anaesthetics. It is easily controlled, and the same vaporizer can be used with a wide range of sizes of subjects. The vaporizer can be placed directly in the respiratory c...
Sisodia CS, Kramer LL, Gupta VS, Lerner DJ, Taksas L.Pharmacological disposition of chloramphenicol was studied in horses. Minimum levels of the antibiotic (greater than or equal to 5 mu g/ml) in blood or plasma recommended to combat infections could not be achieved by 4.4 and 8.8 mg/kg I.V. or 30 and 50 mg/kg I.M. or 30 mg/kg oral (as palmitate salt) doses of chloramphenicol. Increasing the dose to 19.8 and 26.4 mg/kg I.V. provided such levels for about two and three hours respectively. A combination of 20 mg/kg I.V. and 30 mg/kg I.M. administered simultaneously did not provide more prolonged levels than 26.4 mg/kg I.V. alone. Chloramphenicol s...
Mansmann RA.Little has been written about the use of antibiotics in the horse. This article is based on personal experiences related to equine clinical medicine and literature review and certainly does not represent all the possible therapeutic regimens that can he employed in the horse. There are two concepts that this article will emphasize. First and most importantly, when an infective process is suspected in a patient, cul-tures and sensitivities are the most important determinations to be made prior to antibiotic therapy. Whether in the treatment of a single case or in the treatment of a herd problem...
Targowski SP.Treatment of ponies with a single dose of prednisolone markedly reduced the number of blood lymphocytes. A decrease of the number of eosinophils was also observed. In contrast, the number of neutrophils significantly increased. These profound changes were temporary and returned to the pretreatment level within 48 h. The number of monocytes did not show any of the significant changes post-prednisolone treatment. The reactivity of the blood lymphocytes of these ponies, in vitro, to stimulation with phytohemagglutinin (PHA) or streptokinase-strepto-dornase (SK-SD) was measured by incorporation of...
Courtot D, Roux L, Mouthon G, Jeanin E.Doping with tranquilizers has appeared recently in horse-back riding sports. In this paper we study the effects of acepromazine, one of the main tranquilizers used, on various physiological and biochemical aspects of muscular activity (cardiac and respiratory rhythms, seric rates of glucose, urea, protein, creatine phosphokinase, glutamate oxalacetate transaminase, alkaline phosphatase). A low dose (0.02 mg/kg) of acepromazine is injected; the evolution of the variables is studied before and after a standardized effort. After the effort and during recuperation, acepromazine administration caus...
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...
Pyörälä S, Kotilainen T, Silvennoinen P, Hänninen U, Mero M, Kaartinen L.Serum tinidazole concentrations were monitored in five clinically healthy adult horses after intravenous (i.v.) and oral administration of the drug (15 mg/kg and 25 mg/kg, respectively). After i.v. administration, the mean residence time was 7.0 h, the elimination half-life 5.2 h and the body clearance rate 1.6 ml/min/kg. The distribution volume was found to be 660 ml/kg. After oral administration, the mean residence time was 8.5 h, the absorption half-life 1.1 h and the bioavailability essentially 100%. In view of the in-vitro sensitivities of various anaerobic bacteria, a dosage of 10-15 mg/...
Liu Y, Uboh CE, Soma LR, Li X, Guan F, You Y, Rudy JA, Chen JW.Gabapentin (GPT) is an antiepileptic drug that was approved in 1993 for use in the management of neurotrophic pain and as an adjunctive therapy for refractory partial seizure in humans. It is also being tested in veterinary medicine as an adjunctive medication in the treatment of pain due to laminitis, neuropathic, or chronic pain. Gabapentin is readily available by prescription and even on the internet; therefore, it has the potential of being used in racehorses to mask pain. It is for this reason that a sensitive liquid chromatography-tandem mass spectrometry method has now been developed fo...
Wynn MAA, Ball BA, Legacki E, Conley A, Loux S, May J, Esteller-Vico A, Stanley S, Scoggin K, Squires E, Troedsson M.In the latter half of gestation in the mare, progesterone concentrations decline to near undetectable levels while other 5α-reduced pregnanes are elevated. Of these, 5α-dihydroprogesterone and allopregnanolone have been reported to have important roles in either pregnancy maintenance or fetal quiescence. During this time, the placenta is necessary for pregnane metabolism, with the enzyme 5α-reductase being required for the conversion of progesterone to 5α-dihydroprogesterone. The objectives of this study were to assess the effects of a 5α-reductase inhibitor, dutasteride on pregnane metab...
Recchi L, Alvariza S, Benech A, Ruiz N, José Estradé M, Suarez G, Crosignani N.The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean m...
Raisis AL, Hodgson JL, Hodgson DR.Twenty-one compromised neonatal foals hospitalised at the Rural Veterinary Centre (RVC) during 1993 were studied to determine i) serum gentamicin concentrations obtained when gentamicin was administered at 3.3 mg/kg bwt twice daily i.m.; ii) factors which contributed to inter-foal variation in serum gentamicin concentrations achieved and iii) clinical efficacy of gentamicin therapy in foals with confirmed septicaemia. Septicaemia was confirmed in 7 foals with positive blood cultures and suspected in 8 foals with a sepsis score > 11. Peak serum concentrations (Ps) were > 6 microg/ml in al...
Kowalski P, Bieniecki M, Oledzka I, Lamparczyk H.A capillary electrophoretic (CE) method has been developed for the determination of ivermectin (CAS 70288-86-7), a new generation drug with antiparasitic activity, in pig and horse plasma. The method was statistically validated for its linearity, accuracy, precision and selectivity. The linear range was from 1 to 30 ng mL(-1) with correlation coefficients greater than 0.999. The limit of detection was 0.3 ng mL(-1), while the quantitative limit was 1 ng mL(-1), using a 0.5 mL sample size. The validated procedure was used to determination of pharmacokinetic parameters of ivermectin after ingest...
Machnik M, Gerlach M, Kietzmann M, Niedorf F, Thevis M, Schenk I, Guddat S, Düe M, Schänzer W.The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid-liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
Kusano K, Minamijima Y, Mashita S, Kunii H, Yamashita S, Nagata S.Repeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data. Objective: To determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin. Methods: In vivo experimental. Methods: Seven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm , 0.21 g/cm ) for 3 consecutive days. Samples were pretreated by protein precipitation for plas...
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...
Gustafsson K, Tatz AJ, Britzi M, Dahan R, Sutton GA, Kelmer G.Eight horses underwent IVRLP at two occasions through a 23-gauge 2 cm long butterfly catheter. Regional anaesthesia of the ulnar, median and medial cutaneous antebrachial nerves was performed prior, and an 8 cm rubber tourniquet was placed on the proximal radius for 30 minutes following the infusion. The first infusion consisted of 2 g of amikacin sulphate and 10 mg of dexamethasone phosphate diluted with 0.9% NaCl to a total volume of 100 ml. The second perfusion was performed after a 2-week washout period, the same protocol was used but without dexamethasone phosphate. Synovial fluid s...
Lyons ET, Drudge JH, Tolliver SC.Critical tests of the activity on large strongyles, ascarids, mature pinworms, and bots were carried out in 11 horses intraorally treated with a paste formulation of thiabendazole. The dose level of 44 mg/kg was administered to 3 horses, and the dose level of 88 mg/kg to 8 horses. Removals of Strongylus vulgaris and mature Oxyuris equi were 100% at the 2 dose levels, and efficacy against Strongylus edentatus varied from 95 to 99% and 89 to 100% for the 44- and the 88-mg/kg dose levels, respectively. Strongylus equinus was completely removed from the 1 infected horse treated at the dose level o...
Soma LR, Korber K, Anderson T, Hopkins J.The effects of furosemide (0.55 mg/kg IV) on the plasma and urinary fentanyl (PFE UFE) concentrations were studied during steady-state conditions. The PFE during the steady-state period was 0.31 +/- 0.027 ng/ml, with no significant changes occurring, even though the rate of excretion of fentanyl (EX) increased during the 1st hour from 112.0 +/- 21.6 to 534.5 +/- 82.9 ng/minute. The EX returned to control levels within 3 hours, as did the UFE. The injection of furosemide increased glomerular filtration rate from 1.97 +/- 0.21 to 3.81 +/- 0.75 ml/kg/min. The fractional reabsorption decreased fro...
McCann ME, Watson TD, Boudinot FD, Moore JN.We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination...
Yamarik TA, Wilson WD, Wiebe VJ, Pusterla N, Edman J, Papich MG.Using a randomized, cross-over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C(0) was 20.5 μg/mL (±8.8) immediately after i.v. administration. The C(max) was 0.6 μg/mL (±0.36) at T(max) 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half-life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half-life was 3.6 (±1.7) h. The overall mean systemic availability of ...
Schenk I, Broussou D, Roques B, Lagershausen H, Machnik M, Röttgen H, Toutain PL, Thevis M.The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-...
Deaton CM, Marlin DJ, Smith NC, Roberts CA, Harris PA, Kelly FJ, Schroter RC.Vitamin C (ascorbic acid) is a non-enzymatic antioxidant important in protecting the lung against oxidative damage and is decreased in lung lining fluid of horses with airway inflammation. To examine possible therapeutic regimens in a species with ascorbate-synthesising capacity, we studied the effects of oral supplementation of two forms of ascorbic acid, (each equivalent to 20 mg ascorbic acid per kg body weight) on the pulmonary and systemic antioxidant status of six healthy ponies in a 3 x 3 Latin square design. Two weeks supplementation with ascorbyl palmitate significantly increased mean...
Klee S, Nürnberger MC, Keller H, Ungemach FR.A therapeutical dose of kanamycin was tested intravenously and intramuscularly in four normal standardbreds and plasma concentrations were measured over a 12 hour period. Plasma levels exceeded a minimum inhibitory concentration of 4 micrograms/ml within only 15 minutes for 8 hours both after i.v. and i.m. injection. Kanamycin revealed a mean plasma half life of 2.3 hours. Bioavailability of an intramuscular dose was about 76%. The pharmacokinetic parameters demonstrate the rapid onset of antibacterial plasma levels of the test compound. A dose regimen for horses of two times daily 5 mg/kg bod...
Schwarzwald CC, Bonagura JD, Luis-Fuentes V.Quinidine is effective for treatment of atrial fibrillation (AF) in horses, but often accelerates ventricular response rate. Diltiazem effectively controls heart rate response to AF in other species. This investigation determined the effects of diltiazem on cardiac rate and rhythm, left ventricular (LV) function, central hemodynamics, and peripheral blood flow in normal, standing, nonsedated horses. A dose-finding study was performed. Afterward, 8 healthy horses were treated with diltiazem IV every 30 minutes to achieve cumulative dosages of 0 (saline control), 1, 1.5, and 2 mg/kg. Plasma dilt...
Bauer C, Bürger HJ.A paste formulation containing 14.3 per cent of oxibendazole and 44 per cent of trichlorfon was administered to 33 ponies and horses. The dose rate used was equivalent to 10 mg and 30 mg/kg bodyweight, of oxibendazole and trichlorfon respectively. After treatment 25 animals passed between one and 82 third stage larvae of Gasterophilus intestinalis in their faeces. Dosing with 0.2 mg ivermectin/kg bodyweight three weeks later resulted in six animals expelling between one and four bots. The efficacy of the oxibendazole-trichlorfon paste was on average 96.2 per cent. This drug combination given t...
van der Kolk JH, Wisse H, van Dijk S.A 20-year-old Arab crossbred gelding was examined because it had apparently suffered an overstimulation of the parasympathetic nervous system for three hours. The clinical signs consisted of hypersalivation, profuse sweating, maximal miosis, fasciculation of the muscles and lateral recumbency in combination with continuous convulsions without diarrhoea. The horse's plasma pseudocholinesterase activity was approximately 10 per cent of normal. It responded well to 10 mg atropine and 50 mg diazepam administered intravenously.
Ramsay EC, Geiser D, Carter W, Tobin T.To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Methods: Prospective randomized experimental study. Methods: Fifteen adult grade mares weighing 328-537 kg. Methods: The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment a...
Martin EM, Schirmer JM, Jones SL, Davis JL.Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Methods: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses ...
Brumbaugh GW, Thomas WP, Hodge TG.A 4-year-old Quarter Horse gelding with atrial fibrillation, mitral regurgitation, and signs of bilateral congestive heart failure was initially treated IV with digoxin and furosemide. After parenteral digitalization, a daily maintenance dose of digoxin was administered orally at a rate of 21.7 micrograms/kg of body weight. At this dosage, a steady-state serum digoxin concentration of 2.3 ng/ml was achieved without clinical signs of toxicosis. The furosemide dosage was decreased and eventually discontinued as clinical improvement occurred. Clinical signs of congestive heart failure were contro...
Brumbaugh GW, Thomas WP, Enos LR, Kaneko JJ.Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 microgram digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (+/- 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (+/- 0.45) at a mean of 2.29 h (+/- 1.52) after administration. A second rise in serum digoxin concentration started about 6-8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (+/- 5.96). At a dose of 22 microgram digoxin/kg body...
Manohar M, Goetz TE, Sullivan E, Griffin R.The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days...
Garcia P, Paris AC, Leufroy A, Popot MA, Bonnaire Y.A quantitative method, using LC/ESI-MS(n) with a quadrupole linear ion trap mass analyzer, has been developed for the analysis of ipratropium cation in horse plasma and urine. The method applies solid-phase extraction with WCX cartridges for plasma and MM2 cartridges for urine, prior to analysis by LC/ESI-MS(n). The efficiency of extraction combined with the sensitivity and the selectivity of MS(n) allows for the quantification of ipratropium cation at picogram per milliliter levels. The analytical capabilities of the method have been successfully checked by the quantitative analysis of ipratr...
Dirikolu L, Lehner AF, Hughes C, Karpiesiuk W, Camargo FC, Harkins JD, Woods WE, Bosken JM, Boyles J, Troppmann A, Fisher M, Tobin T.Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine th...
Cunningham FM, Andrews M, Landoni MF, Lees P.Calcium ionophore A23187 induced time and concentration dependent production of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5-lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore-induced LTB4 synthesis by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30 +/- 0.75 microM for BAY Y 1015 and BAY X 1005, r...
Werners A, Karasek I, Butler C, Yeatts J, Enomoto H, Baynes R.Several different tick species are known to infest horses. Aside from causing serious health and welfare issues, including anaemia, ill thrift, and immunosuppression, ticks can transmit a variety of important, sometimes zoonotic, pathogens. The successful prevention and treatment of tick infestations have been described, but the information is scarce and, in many instances, anecdotal. Here we describe a practical and affordable prevention of tick infestation by using abamectin-impregnated cattle ear tags affixed to a safety collar. We have assessed the radial distribution of abamectin by analy...
Hagedorn HW, Meiser H, Zankl H, Schulz R.The misuse of opiates in racehorses relates to their effect of increasing locomotor activity. Because methadone, a narcotic analgesic, has been suspected of use as a doping compound in the past, it was added to the list of banned drugs and should be considered in doping control. Because the literature fails to provide information on detection of methadone in blood or urine of horses, an enzyme-linked immunosorbent assay was developed to monitor this narcotic in equine body fluids. Combined with high-performance liquid chromatography, the immunoassay also served to confirm positives indicated b...
