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.
Andrews FM, Sifferman RL, Bernard W, Hughes FE, Holste JE, Daurio CP, Alva R, Cox JL.Equine gastric ulcer syndrome (EGUS) is very common among performance horses, with a reported prevalence of approximately 90% in racehorses, and also > 50% in foals. Omeprazole, an acid pump inhibitor 5 times more potent than ranitidine, has been used with great success to treat EGUS. This multicentre study of Thoroughbred racehorses with endoscopically verified gastric ulcers was designed to demonstrate the efficacy of an equine oral paste formulation of omeprazole in the treatment and prevention of recurrence of EGUS. Of the 100 horses entered into the study, 25 were sham-dosed for the full ...
Vatistas NJ, Snyder JR, Nieto J, Thompson D, Pollmeier M, Holste J.Gastric ulceration has been found to occur in 80-90% of Thoroughbreds in active race training. Previously, variable success has been reported using mucosal surface protectants and H2 receptor antagonist. Omeprazole, a substituted benzimidazole, has been shown to inhibit gastric acid secretion in both man and animals. Fourteen horses, in active race training and with endoscopic evidence of moderated to severe gastric ulceration were divided into 2 groups: Group 1 (7 horses) were given placebo paste orally once daily for 28 days; Group 2 (7 horses) received 1.54 g active omeprazole in the placeb...
Plue RE, Wall HG, Daurio C, Attebery DK, Cox JL, Wallace DH.Omeprazole has been shown to promote healing of spontaneously occurring gastric ulcers in horses when administered for 28 days at a dose of 4 mg/kg bwt/day and to prevent recurrence of ulcers in almost all horses when treatment is continued at a dose of at least 2 mg/kg bwt/day. The purpose of the 3 studies reported here was to 1) evaluate the evolution of potential effects of omeprazole paste (GastroGard), at a dose of 20 mg/kg bwt/day (5x the recommended dose) for 91 days in mature Thoroughbred horses; 2) evaluate the safety in young horses of omeprazole paste when dosed at 4 mg/kg bwt/day (...
Daurio CP, Holste JE, Andrews FM, Merritt AM, Blackford JT, Dolz F, Thompson DR.In a multicentre trial, 13 cannulated horses were treated orally once daily with a paste that delivered omeprazole at a dose of 4 and 5 mg/kg bwt in a 2-period crossover design to evaluate steady state gastric acid suppression. In each period, basal (unstimulated) and pentagastrin-stimulated gastric output were evaluated at 5-8 h after 5 doses, at 13-16 h after 10 doses, and at 21-24 h after 15 doses. Baseline data for gastric acid secretion were collected once for each horse in the month prior to initiation of omeprazole treatment. The inhibition of gastric acid secretion relative to baseline...
Haven ML, Dave K, Burrow JA, Merritt AM, Harris D, Zhang D, Hickey GJ.The antisecretory activity of omeprazole on gastric acid when administered i.v., intragastrically or per os, was evaluated in 2 female and 3 castrated male horses. Each horse had been prepared with a chronic indwelling gastric cannula. A single i.v. administration of omeprazole (1.5 mg/kg bwt) was effective in abolishing basal and pentagastrin (PG)-stimulated acid secretion. Once daily, nasogastric administration of omeprazole in acid-stable granules for 5 days inhibited acid secretion in a dose-dependent manner: 57% (1.5 mg/kg bwt) and 98% (5.0 mg/kg bwt) reduction of PG-stimulated acid secre...
Sandin A, Andrews FM, Nadeau JA, Doherty TJ, Nilsson G.The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was 2.1-4....
Carlson GP, Jones JH.This study was undertaken to evaluate the effects of frusemide on the concentration of plasma electrolytes and the relationship between changes in electrolyte concentration and the simultaneous changes in acid-base balance in arterial and venous blood during intense exercise. Five exercise-conditioned Thoroughbred horses were exercised on a high-speed treadmill at a slope of 10% at speeds known to exceed VO2max. Horses participated in 3 randomised exercise trials in which they received either placebo (control), low-dose frusemide (0.5 mg/kg bwt), or high-dose frusemide (1.0 mg/kg) 4 h prior to...
Buchner HH, Kübber P, Zohmann E, Peham C.A kinematic study was performed to establish the locomotion pattern of horses under detomidine sedation and the effects of antagonization for possible use during lameness examinations in uncooperative horses. The kinematics of 17 Warmblood horses (9 sound, 8 lame with chronic forelimb lameness) were recorded on 2 days using a high-speed video system while trotting (3.9 m/s) on a treadmill. On each day a control measurement was carried out prior to sedation with detomidine (10 micrograms/kg bwt) and repeated recordings at 15, 25, 35, 45 and 60 min after sedation. On the second day, sedation was...
Gleed FD, Ducharme NG, Hackett RP, Hakim TS, Erb HN, Mitchell LM, Soderholm LV.We hypothesised that frusemide would decrease pulmonary capillary pressure in horses during strenuous exercise. Seven horses were tested after receiving saline or frusemide (2 mg/kg bwt) in random order with an interval of at least one week. Measurements were made with the horses standing, exercising at 75, 90 and 100% HRmax (maximal heart rate), and then walking 2 min after cessation of 100% HRmax. The exercise tests lasted for approximately 3 min with an interval of walking between them. Pulmonary artery and oesophageal pressures were recorded continuously and subsequent analysis of the pulm...
Goetz TE, Manohar M, Magid JH.The objective of the present study was to ascertain whether administration of a second dose of frusemide would attenuate exercise-induced pulmonary hypertension more than a single dose. Right atrial, right ventricular and pulmonary vascular pressures were determined in 7 healthy, sound, exercise-trained Thoroughbred horses at rest and during exercise (14.2 m/s + a 3.5% uphill grade) performed at maximal heart rate (217 +/- 3 beats/min [mean +/- s.e.]). Horses were studied during the following 3 treatments in random order 7 days apart: control (no medication), frusemide single dose (250 mg i.v....
Dirikolu L, Lehner F, Nattrass C, Bentz BG, Woods WE, Carter WG, Karpiesiuk W, Jacobs J, Boyles J, Harkins JD, Granstrom DE, Tobin T.Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral ...
Nollet H, Van Loon G, Deprez P, Sustronck B, Muylle E.To establish reference values for right ventricular maximal rate of increase in pressure (dP/dt(max)) in horses and determine the usefulness of this variable to evaluate cardiac contractility. Methods: 15 crossbred horses, 3 to 20 years old. Methods: Cardiac catheterization was performed, using a high-fidelity catheter tip micromanometer, to determine right ventricular dP/dt(max). The following mathematic corrections were made: for preload, (dP/dt(max))/instantaneous total pressure, (dP/dt(max))/instantaneous developed pressure, and (dP/dt(max))/end diastolic pressure; for afterload, (dP/dtCPI...
Todi F, Mendonca M, Ryan M, Herskovits P.The origin of caffeine detections in equine serum and urine after theophylline administrations was examined. Three different preparations containing theophylline were administered to standardbred mares. Both blood and urine samples were collected. Caffeine was detected and quantified in theophylline administration samples by high performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). Further in vitro analysis showed that caffeine metabolites were not detected when caffeine, or caffeine-containing products, were added to urine. Data derived from ...
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...
Dowling PM.The well-developed defense barriers of the CNS and the expense of drug therapy limit the pharmacologic options for the treatment of neurologic diseases in horses. New approaches to controlling inflammation in the CNS are improving the outcomes of bacterial meningitis. The appropriate treatment of EPM remains controversial. More research is needed to evaluate the pharmacokinetics and pharmacodynamics of drugs in the CNS of the horse. Behavioral pharmacology has become fashionable in human and small animal medicine, but it needs to be evaluated for the potential of unethical use in performance h...
Whittem T.This article presents in easily accessible form a collection of drug names and dose rates for the drugs recommended or referred to by the authors of the individual articles in this issue. Although the formulary provides recommendations for drug use, the reader is cautioned that the responsibility for the choice of agent, formulation, dose, and dose interval lies with the clinician. The author also addresses regulations that govern the use of drugs in competition horses.
Mogg TD.Cardiac disease is often life-threatening and challenging to treat. Prolonged therapy is indicated in many cases, which can lead to problems with treatment costs, owner compliance, and potential drug toxicity. Many therapies are empirical or based on data from other species because of a lack of well-designed prospective clinical trials in horses. This article reviews the clinical pharmacology and therapeutics of heart failure, cardiac arrhythmias, myocardial disease, endocarditis, and pericardial disease.
Wichtel ME, Buys E, DeLuca J, Stringel G.This article focuses on the pharmacologic properties of drugs commonly used in the treatment of neonatal septicemia and its complications. Rational therapy demands an awareness of not only the pharmacology of individual drugs but also the interactions and anticipated fate of such drugs in the rapidly changing physiologic environment of the neonate. Further research in the area of equine neonatal pharmacology should greatly assist our understanding of the impact of the disease state on the unique physiology of the newborn and should allow us to better predict the ultimate fate of drugs commonly...
Jose-Cunilleras E, Hinchcliff KW.Pharmacologic treatment of diseases of the urinary tract of horses is limited to administration of antibiotics for treatment of urinary tract infections (UTIs), administration of drugs that alter urine pH, administration of drugs that alter bladder smooth muscle function or urethral sphincter tone, and treatment of acute renal failure. The indications, mechanisms of action, pharmacokinetic characteristics, and adverse effects of these agents in each of these groups are discussed in this article. The use of the agents is discussed within the context of the pathophysiology of the disease being t...
Anderson BH, Ethell MT.A number of methods for the local delivery of drugs to musculoskeletal tissues in the horse are now available. Further research is required to document the disposition of drugs delivered by such methods and to correlate this information with efficacy. Perhaps the greatest potential area for the methods discussed is the treatment of synovial and bone infections. To be able to provide high and sustained therapeutic concentrations of antimicrobials to the site of infection should increase the chances of success in such cases. These methods of drug delivery need to be used in conjunction with othe...
Coakley M, Peck KE, Taylor TS, Matthews NS, Mealey KL.To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
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...
Auvray P, Sourdaine P, Moslemi S, Séralini GE, Sonnet P, Enguehard C, Guillon J, Dallemagne P, Bureau R, Rault S.In this study, we describe the synthesis of a new family of indolizinone derivatives designed to fit an extrahydrophobic pocket within the active site of aromatase and to strongly inhibit human aromatase. This could help improve the specificity of the inhibitors. Equine aromatase, very well characterized biochemically, is used as a comparative model. Indeed, in a previous comparison between both human and equine aromatases, we described the importance of the interaction between the inhibitor and this pocket for the indane derivative MR 20814. MR 20492 and MR 20494 are more potent inhibitors of...
Jaraiz MV, Rodriguez C, San Andres MD, Gonzalez F, San Andres MI.Suxibuzone (SBZ), a nonsteroidal anti-inflammatory drug, was administered to 6 horses at a dose rate of 7.5 mg/kg bwt by intravenous (i.v.) route. Plasma and synovial fluid concentrations of suxibuzone and its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ), were measured simultaneously by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Plasma SBZ concentrations rapidly decreased and were not detectable beyond 20 min after treatment. The parent drug was not detected in...
Corveleyn S, Henrist D, Remon JP, Van Der Weken G, Baeyens W, Haustraete J, Aboul-Enein HY, Sustronck B, Deprez P.Ketoprofen (KTP) is a chiral non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class, approved by the FDA for the allevation of pain associated with musculoskeletal disorders in horses. The present study was designed to examine the bioavailability of ketoprofen enantiomers after rectal administration of the racemate to healthy horses. One gram of racemic ketoprofen was injected intravenously and administered rectally as a fat based suppository in a cross-over design study (n = 4). Blood samples were analysed for KTP enantiomers using HPLC. After IV administration, the S(+) ena...
Jaraiz V, Rodriguez C, San Andres MD, Gonzalez F, San Andres MI.A disposition and bioequivalence study with a suxibuzone granulated and a suxibuzone paste oral formulation was performed in horses. Suxibuzone (SBZ) is a nonsteroidal anti-inflammatory drug, which was administered to horses (n = 6) at a dosage of 19 mg/kg bwt by the oral route (p.o.) in a two period cross-over design. Suxibuzone is very rapidly transformed into its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefore plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simultaneously measured by a sensitive and specific high-performance liquid chro...
Doherty TJ, Andrews FM, Provenza MK, Frazier DL.The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. Methods: Prospective randomized experimental study. Methods: Six adult ponies, 135 to 275 kg. Methods: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tm...
Breuhaus BA, DeGraves FJ, Honore EK, Papich MG.To determine pharmacokinetics of ibuprofen in healthy foals and to determine clinical effects after oral administration for 6 days. Methods: 7 healthy 5- to 10-week-old foals. Methods: Serum concentrations of ibuprofen were measured after IV and oral (nasogastric tube) administration at dosages of 10 and 25 mg/kg of body weight. Foals were given ibuprofen (25 mg/kg, PO, q 8 h) as a paste for 6 days. Serum and urine were obtained before and after the 6-day period. Results: Half-life of elimination (Kel t1/2) of IV-administered ibuprofen (ie, 10 and 25 mg/kg), was 79 and 108 minutes, maximal ser...
Sams RA, Gerken DF, Ashcraft SM.The objectives of the study were to compare various methods to determine flunixin in test samples collected periodically from horses after intramuscular (IM) and intravenous (IV) dosing at the maximum recommended dosage and to document detection times for this drug in test samples. Flunixin, a nonsteroidal anti-inflammatory drug approved for use in horses, was administered to eight mares in five consecutive daily doses of 1.1 mg per kilogram of body weight by the IM or IV route. Flunixin was detected in urine samples collected at various times after drug administration by flunixin enzyme-linke...
Letendre L, Kvaternick V, Tecle B, Fischer J.A rugged, sensitive and efficient liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative analysis of firocoxib in urine from 5 to 3000 ng/mL and in plasma from 1 to 3000 ng/mL. The method requires 200 microL of either plasma or urine and includes sample preparation in 96-well solid phase extraction (SPE) plates using a BIOMEK 2000 Laboratory Automated Workstation. Chromatographic separation of firocoxib from matrix interferences was achieved using isocratic reversed phase chromatography on a PHENOMENEX LUNA Phenyl-Hexyl column. The mobile phase w...
Chui YC, Esaw B, Laviolette B.Urine samples collected from a horse after intramuscular administration of 40 mg of azaperone were extracted at pH 10 before and after acid hydrolysis. The extracts were concentrated and analysed by LC-MS-MS. Two N-dealkylated metabolites, N-despyridinylazaperol and N-despyridinylazaperone, and a low concentration of azaperone were detected in the unhydrolysed urine. Six metabolites; hydroxyazaperol, two hydroxyazaperones, azaperol, N-despyridinylazaperol and N-despyridinylazaperone were detected in the hydrolysed urine extracts. Using XAD-2 resin extraction, three glucuronide conjugated azape...
Mirra A, Birras J, Diez Bernal S, Spadavecchia C.Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictab...
Dumasia MC, Houghton E, Hyde W, Greulich D, Nelson T, Peterson J.Studies related to the in vivo biotransforrmation and urinary excretion of fenspiride hydrochloride in the horse are described. After oral administration, the drug is metabolised by both phase I functionalisation and phase II conjugation pathways. Following enzymatic deconjugation, fenspiride and its phase I metabolites were isolated from post-administration biofluids using bonded co-polymeric mixed mode solid-phase extraction cartridges to isolate the basic compounds. Following trimethylsilylation (TMS), the parent drug and metabolites were identified by capillary gas chromatography-mass spec...
Plue RE, Wall HG, Daurio C, Attebery DK, Cox JL, Wallace DH.Omeprazole has been shown to promote healing of spontaneously occurring gastric ulcers in horses when administered for 28 days at a dose of 4 mg/kg bwt/day and to prevent recurrence of ulcers in almost all horses when treatment is continued at a dose of at least 2 mg/kg bwt/day. The purpose of the 3 studies reported here was to 1) evaluate the evolution of potential effects of omeprazole paste (GastroGard), at a dose of 20 mg/kg bwt/day (5x the recommended dose) for 91 days in mature Thoroughbred horses; 2) evaluate the safety in young horses of omeprazole paste when dosed at 4 mg/kg bwt/day (...
Nourian AR, Mills PC, Pollitt CC.Microdialysis (MD) was used for continuous monitoring of the lamellar extracellular fluid (ECF) in six mature healthy Standardbred horses. MD probes were introduced into the lamellar tissue under local anaesthesia. Following intravenous injection of gentamicin (5mg/kg), MD and serum samples were collected for 24h and analysed using a sensitive ELISA test for gentamicin and fluorescence polarization immunoassay for urea concentrations. Calibration of probes was performed through in vivo urea recovery and in vitro gentamicin and urea recovery. Data obtained from different body compartments were ...
Pusterla N, Hall TL, Wetzlich SE, Monmaney G, Collier JR, Hill JA, Tell LA.The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the...
Wotman KL, Utter ME.To assess the effect of treatment with a topical ophthalmic preparation of 1.2% nalbuphine solution on corneal sensitivity in clinically normal horses. Methods: 8 horses. Methods: Baseline corneal touch threshold (CTT) was measured (defined as the mean filament length [mm] at which a consistent blink response was elicited) for both eyes of each horse by use of a Cochet-Bonnet aesthesiometer. Subsequently, 0.2 mL of 1.2% nalbuphine solution was instilled in 1 randomly selected eye of each horse, and 0.2 mL of artificial tears solution was instilled in the contralateral eye (control treatment). ...
Danek J.Four clinically normal stallions were infused intravenously with endotoxin (LPS) from Escherichia coli 055:B5 at a dose of 0.3 microg/kg b.w. and four stallions were treated with flunixin meglumine (FM) as a single intravenous injection at a dose of 1.1 mg/kg b.w., 5 min after the infusion of LPS. In response to endotoxin infusion, stallions' reaction was fever (increased rectal and scrotal skin temperature), increased heart rate (HR) and leucopenia. Administration of endotoxin also influenced the level of testosterone (decrease at 3-24 h and increase at 48-72 h after LPS administration) in th...
Mills PC, Dunnett M, Smith NC.The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e(-25.14t) + 159.93e(-10.96t) for allopurinol and Cp = 321.09e(-9.72t) + 82.39e(-0.44t) for oxypurinol, with an elimination half-life (t1/2 beta) of 0.09 h and an area under the curve (AUC) of 19.8 mumol.h/L after intravenous administration, while the t1/2 beta and AUC of oxypurinol were 1.09 h and 231 mumol.h/L, respec...
Yocom A, Contino E, Kawcak C.Bisphosphonates are a group of drugs that can reduce bone resorption by incorporating into the crystal structure of exposed hydroxyapatite where they are taken up by osteoclasts. Bisphosphonates have several other mechanisms of action including reducing pain and inflammation and altering macrophage function. There are two types of bisphosphonates-nitrogenous and non-nitrogenous, the latter of which is used in horses. This article provides a literature-based review of the proposed mechanisms of action and therapeutic uses of bisphosphonates including a brief review of bone response to disease. ...
Moeller BC, Sams RA, Guinjab-Cagmat J, Szabo NJ, Colahan P, Stanley SD.Testosterone is an anabolic androgenic steroid (AAS) that is endogenously produced by both male and female horses that also has the potential for abuse when administered exogenously to race horses. To recommend appropriate withdrawal guidelines so that veterinarians can discontinue therapeutic use prior to competition, the pharmacokinetics and elimination of testosterone were investigated. An aqueous testosterone suspension was administered intramuscularly in the neck of Thoroughbred horses (n = 20). The disposition of testosterone from this formulation was characterized by an initial, rapid a...
Natalini CC, Linardi RL.To evaluate the effects of epidural administration of hydromorphone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Methods: 6 healthy adult horses. Methods: Horses were assigned to receive hydromorphone (0.04 mg/kg) or a control solution (20 mL of sterile water) administered epidurally into in the first intercoccygeal space. Treatments were administered at time intervals of > or = 7 days. Electrical stimulation was applied for 6 hours after epidural injection over the dermatomes of the perineal, sacral, lumbar, and t...
Pascoe PJ, Black WD, Claxton JM, Sansom RE.The pharmacokinetics of alfentanil were investigated in the horse. Four doses of alfentanil (4, 10, 20 and 40 micrograms/kg) were given to four horses at different times and their locomotor activity monitored. Doses of 20 and 40 micrograms/kg produced a significant increase in locomotor activity. The plasma concentrations of alfentanil were measured in six standing horses and the pharmacokinetics calculated. It was found that the decay curves were best described by a biexponential equation. The elimination half-life (t1/2 beta) was 21.65 +/- 3.99 min and the clearance (Cl) was 14.1 +/- 0.7 ml/...
Ensink JM, Moi A, Vulto AG, Tukker JJ.Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the...
Mas M, Mañé N, Fernández F, Gallego D, Pumarola M, Jiménez M.In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) follo...
Trim CM, Moore JN, White NA.Dopamine hydrochloride was infused intravenously into six horses anaesthetised with halothane. Three dose rates; 0.5, 2.5 and 5.0 micrograms/kg/min, were evaluated in each horse. The cardiac output was significantly increased at 15 and 30 mins following administration of dopamine at 2.5 and 5.0 micrograms/kg/min. The heart rate, facial artery pressure and pulmonary artery pressure remained unchanged. Total peripheral resistance was significantly decreased at 30 mins with 2.5 micrograms/kg/min and at 15 and 30 mins with 5.0 micrograms/kg/min. No significant change was produced in packed cell vo...
Gokbulut C, Nolan AM, McKellar QA.Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite i...
Soma LR, Uboh CE, Rudy J, Fegely J.The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2 (TxB2) concentrations were studied in sedentary and 2-year-old horses in training. The baseline TxB2 serum concentrations generated during clotting were 2.89 +/- 0.81, 2.19 +/- 0.25 and 0.88 +/- 0.12 ng/ml for the 2-year-old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2 concentrations between older and younger horses (P less than 0.005). Significant reduction in TxB2 production from baseline wer...
Soma LR, Uboh CE, Rudy JA, Perkowski SZ.Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after IV administration in horses. The plasma disposition, after IV administration of 5 mg/kg of body weight, was described by a two-compartment model; mean +/- SD distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56 hours, respectively. Plasma concentration of naproxen...
Coyne CP, Hornof WJ, Kelly AB, O'Brien TR, DeNardo SJ.Two methods were analyzed for the rapid extraction of equine fibrinogen from fresh plasma, using ammonium sulfate-sodium phosphate buffer. Fibrinogen from each of these 2 methods was then radiolabeled with 125I (half-life = 60.2 days, gamma = 35 keV), using monochloroiodine reagent. Mean protein-bound activity was 98.5% and mean clottable radioactivity was 94.1%. Radiolabeled fibrinogen administered IV to 15 horses had an overall mean (+/- SD) plasma half-life of 4.95 +/- 0.44 days.
Czerwinski SL, Lyon AW, Skorobohach B, Léguillette R.Ophthalmic antibiotic therapy in large animals is often used empirically because of the lack of pharmacokinetics studies. The purpose of the study was to determine the pharmacokinetics of topical tobramycin 0.3% ophthalmic solution in the tears of normal horses using an automated immunoassay analysis. Results: The mean tobramycin concentrations in the tears at 5, 10, 15, 30 minutes and 1, 2, 4, 6 hours after administration were 759 (±414), 489 (±237), 346 (±227), 147 (±264), 27.6 (±28.4), 14.8 (±66.6), 6.7 (±18.6), and 23.4 (±73.4) mg/L. Mean tobramycin concentration was maintained abo...
Lakritz J, Wilson WD, Marsh AE, Mihalyi JE.To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals. Methods: 6 healthy foals, 3 to 5 months old. Methods: Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of eryth...
Steel CM, Bolton JR, Preechagoon Y, Charles BG.The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by...
Baeyens WR, Van der Weken G, Haustraete J, Aboul-Enein HY, Corveleyn S, Remon JP, García-Campaña AM, Deprez P.The group of LiChrospher ADS (alkyl-diol silica) sorbents that make part of a unique family of restricted-access materials, have been developed as special packings for precolumns used in the LC-integrated sample processing of biofluids. The advantage of these sorbents lies in the direct injection of untreated biological fluids, that is without sample clean-up, the elimination of the protein matrix with a quantitative recovery together with an on-column enrichment. The present method is based on previous work applying UV detection at 260 nm for ketoprofen determinations. Plasma samples introduc...
Taylor P, Scarth JP, Hillyer LL.Within equine drug surveillance, there is significant interest in analyzing intact phase II conjugates of drugs in urine, but progress has been limited by a lack of reference material. Methods: In this study, in vitro techniques using equine liver fractions were employed to produce glucuronide and sulfate conjugates of stanozolol, 16β-hydroxystanozolol and nandrolone, the glucuronide conjugate of morphine and the glutathione metabolite of chlordinitrobenzene for the first time in equine sports drug surveillance. Results: The glucuronide conjugate of the synthetic progestagen altrenogest was a...
Burrows GE, MacAllister CG, Ewing P, Stair E, Tripp PW.The effects of time and method of administration of rifampin with respect to feeding were evaluated in five mature horses. There was a significant (P less than or equal to 0.05) delay in time of maximum serum concentration and an apparent but not significant decrease in oral absorption when rifampin was given as a top dressing on grain as compared with administration in corn syrup 2 h before or 2 h after feeding. Although there were no differences between administration before or after feeding, administration 2 h prior to feeding was selected as the method of choice for future experiments. The...
Daels PF, Besognet B, Hansen B, Mohammed H, Odensvik K, Kindahl H.To determine the role of progesterone in the regulation of endogenous prostaglandin F2 alpha (PGF2 alpha) secretion during cloprostenol-induced abortion and to investigate use of progestins to prevent prostaglandin-associated abortion. Methods: 16 pregnant mares. Methods: To induce abortion, cloprostenol (250 micrograms/d) was administered daily until fetal expulsion or for up to 5 days. In experiment 1, 8 mares, 98 to 153 days' pregnant, received progesterone (300 mg/d) at 24-hour intervals for 5 days, starting 18 hours after the first cloprostenol administration. In experiment 2, 8 mares, 93...
Haywood PE, Teale P, Moss MS.Thoroughbred geldings were fed racehorse cubes containing a predetermined concentration of theobromine in the form of cocoa husk. They were offered 7 kg of cubes per day, divided between morning and evening feed, and food consumption was monitored. Urinary concentrations of theobromine were determined following the consumption of cubes containing 11.5, 6.6, 2.0 and 1.2 mg per kg of theobromine, to verify whether or not such concentrations would produce positive urine tests. Pre-dose urine samples were collected to verify the absence of theobromine before each experiment. It became apparent fro...
Kitzman JV, Wilson RC, Booth NH, Hendricks HL, Bush PB.The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volu...
