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.
Drudge JH, Lyons ET, Tolliver SC.Critical tests were carried out in 10 horses to evaluate the antiparasitic activity of febantel given alone or with trichlorfon. Paste formulations were administered intraorally at dose levels of 6 mg of febantel (active ingredient)/kg and 35 mg of trichlorfon (active ingredient)/kg. In 5 tests with febantel alone, removal of 100% was recorded for mature or immature Parascaris equorum from 2 infected horses. Strongylus vulgaris from 4 infected horses, S edentatus from 5 infected horses, and mature Oxyuris equi from 1 infected horse; and removal of 96% was recorded for small strogyles from 1 ho...
Allen WE.Plasma concentrations of sodium benzylpenicillin were measured following intrauterine infusion at a dose rate of 22,000 u/kg (250,000 u/ml). The reproductive status of the mare at the time of infusion did not appear to influence plasma concentrations of penicillin, but preswabbing the endometrium for bacteriological culture resulted in peak plasma concentrations which were nearly twice those found in unswabbed mares.
Allen WE, Clarke AR.Plasma concentrations of sodium benzylpenicillin following intrauterine infusion were increased by reducing the volume of solution and expelling air from the vagina after infusion. Instillation of 10 per cent Lugol's iodine solution into the uterus before penicillin infusion further increased the absorption rate, although peak plasma levels of penicillin were less than half those which resulted from intramuscular injection of the same dose.
Powis G, Snow DH.There are now several examples showing that experimentally induced changes in hepatic blood flow can have a marked effect upon the elimination of certain high clearance drugs. Changes in hepatic blood flow produced by exercise might therefore be expected to influence the clearance of these drugs. There was an increase of up to 100%, compound to control values, in the plasma levels of propranolol in horses given either d- or dl-propranolol, 0.2 mg/kg b.wt., and then subjected to sustained exercise for 30 minutes. There was, however, no similar increase with exercise in the plasma levels of anti...
Pearson H, Weaver BM.The paper reports 6 cases of priapism with subsequent protrusion and paresis after neuroleptanalgesia and anaesthesia in horses. Five were ultimately treated by amputation of the penis but the sixth horse is responding satisfactorily to conservative treatment at the time of writing. Causative factors, preventive measures and possible methods of treatment are discussed.
Boersema JH.A horse with foot-mange failed to recover following a number of courses of treatment with coumaphos. Mites isolated from this horse were tested in vitro for their sensitivity to coumaphos and lindane. The mites were resistant to coumaphos and sensitive to lindane. Following treatment with lindane, the horse recovered within four weeks.
Bergan T, Versland I.To be active, antimicrobials must reach the bacteria in the infectious foci in adequate concentrations. Direct measurements of levels in the various foci are difficult to perform, but a number of animal models with artificial extravascular foci have been developed. In many ways, the physiology of pigs resemble that of humans. Consequently, it was thought that pigs might also parallel humans in the handling of penicillins. General pharmacokinetics of ampicillin and flucloxacillin and the penetration of the substances to subcutaneously implanted teflon tistisue chambers were investigated. Ampici...
Steffey EP, Howland D.The slow rate of change of inspired halothane concentration which results in a conventional large animal circle anesthetic delivery system when low carrier gas flow rates are used was confirmed, using a model system. To obtain a 63% change in inspired halothane concentration in the 32-L large animal circle anesthetic machine at fresh gas inflow rates of 3, 6, and 12 L/minute required 10.7, 5.3, and 2.7 minutes, respectively. At a given inflow rate, increasing the rebreathing bag size from 20 to 40 L prolonged the time for equilibration between the gas flowing into the anesthetic circuit and th...
Sasse HH, Hajer R.The manufacturers state that NAB 365 is a beta2-receptor-stimulating sympathicomimetic agent. According to the medical literature it combines a bronchial antispasmodic effect with certain bronchia secretolytic properties and has few untoward side-effects on, for instance, the heart and intestine. The effectiveness of administration of NAB 365 in horses with chronic or acute respiratory disease was tested in the Department of Veterinary Internal medicine in Utrecht. NAB 365 administered at a dosage of 0.8 gamma/kg, of body weight was found to have a marked bronchodilative effect in horses. Ther...
Drudge JH, Lyons ET.The critical test is the primary method used for the efficacy evaluation of drugs against the major internal parasites (bots, ascarids, large strongyles, small strongyles, and pinworms) of the horse. The critical test determines: (1) spectrum of activity, (2) effectiveness of removal, (3) pattern of discharge, and (4) physical condition of each species of these parasites. General characteristics of the major parasitisms of the horse are discussed briefly. Criteria of the critical test also are considered including: (1) number of tests, (2) strain variation and drug resistance, (3) selection of...
Duncan JL, McBeath DG, Best JM, Preston NK.The efficacy of fenbendazole against immature stages of Trichonema spp., Strongylus vulgaris and Strongylus edentatus was evaluated. Naturally infected 6 to 12 month old ponies were given single, oral doses of 0, 15, 30 and 60 mg/kg of body weight. A dose response relationship was noted between increasing dose levels and efficiency against larval trichonemes and migrating stages of S. vulgaris and S. edentatus. Dose levels of 30 mg/kg and higher removed 93 per cent of mucosal stages of Trichonema spp., while doses of 60 mg/kg removed 83 per cent and 89 per cent of the migrating larvae of S. vu...
Steffey EP, Howland D, Giri S, Eger EI.The minimal alveolar concentration of anesthetic required to prevent gross purposeful movement in response to electrical stimulation of oral mucous membranes was determined in horses for 3 agents. Equipotent concentrations of enflurane were 2.12 volumes %; of halothane, 0.88 volumes %; and of isoflurane, 1.31 volumes +. The alveolar concentration required to produce at least 60 seconds of apnea was also determined for these agents. From these data and the minimal alveolar concentration information, anesthetic indices were determined for each agent. The indices for enflurane, halothane, and iso...
Beech J, Kohn C, Leitch M, Weinstein AJ, Gallagher M.Serum, synovial fluid, and urine concentrations of gentamicin were measured in normal mature horses which had been given a single dose of the drug. Mean peak serum concentration (16.8 microgram/ml) occurred in horses 30 minutes after they were given a single intramuscular dose of 4.4 mg of gentamicin/kg of body weight. In horses given a smaller dose of gentamicin (1.7 mg/kg), mean peak serum concentrations of gentamicin (10.2 microgram/ml) appeared at 1 hour. Synovial fluid concentration was maximum at 2 hours for both doses; in horses given the larger dose, mean peak concentration was 6.4 mic...
Kwok WH, Choi TLS, Leung GNW, Wong ASY, Yue SK, Wan TSM, Ho ENM.The insulin-like peptide relaxin (RLX), an endogenous peptide hormone produced in human for pregnancy and reproduction, is also known to exert a range of physiological and pathological effects. Its use is banned in human sports, horseracing, and equestrian competitions due to its potential performance enhancing effect through vasodilation resulting in the increase of blood and oxygen supplies to muscles. Little is known about the biotransformation and elimination of RLX in horses. This paper describes an administration study of rhRLX-2 and its elimination in horses, and the development of sens...
McKeever KH.This article has presented information on the importance of the sympathetic nervous system in the response to exercise. The authors have reviewed the very limited information on the effects of sympathomimetic and sympatholytic drugs on exercise performance in the horse. Most of these drugs are specifically prohibited under the rules of racing, and they have significant side effects that either decrease performance or make their use dangerous to both the horse and horse-man. Additionally, all of these drugs or their metabolites are readily detected by current drug testing protocols. Further inf...
Popot MA, Donval A, Bonnaire Y, Huau J.Feces are a possible medium to be used for horse doping control. Efficient methods for detecting drugs in feces collected from various animals are routinely applied in institutes of food safety in Belgium. We have already tested whether they are applicable to horse feces. In this report, accelerated solvent extraction (ASE), an efficient method for extracting compounds from solid material, has been tested. ASE has been used to replace the diethyl ether liquid-liquid extraction step present in the method initially set up. This technique has been optimized for detecting several non-steroidal ant...
Errecalde JO, Landoni MF.The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2 beta) was 16.91 +/- 0.93 h, the apparent volume of distribution (Vd) was 1.35 +/- 0.18 L/kg and the body clearance (ClB) was 0.061 +/- 0.009 L kg-1 h. After oral administration the half-life of absorption was 1.24 +/- 0.30 h, and the calculated bioavailability was above 100%. The t1/2 beta after oral administration was 18.51 +/- 1.75 ...
McDonald J, Gall R, Wiedenbach P, Bass VD, DeLeon B, Brockus C, Stobert D, Wie S, Prange CA, Yang JM.We investigated the use of particle concentration fluorescence immunoassay (PCFIA) as a technique for drug detection in racing horses. The test was constructed from an antiserum to a carboxyfentanyl-BSA conjugate and carboxyfentanyl linked to b-Phycoerythrin. Using these reagents and a PCFIA apparatus levels of fentanyl as low as 0.1 ng/ml could be detected by the assay. In addition, cross-reactivity studies on this assay showed that the anti-serum cross-reacted well with carfentanil, sufentanil and the methylated analogs of fentanyl. We therefore evaluated the ability of these agents to produ...
Fuentes VO, Gonzalez H, Sanchez V, Fuentes P, Rosiles R.The toxic effect of neomycin on the horse kidney was studied. Twelve horses were used, and were divided at random into three groups of four. The first group was treated twice a day with 10 mg/kg I.M. for 15 days and then euthanised; kidney and liver samples were studied and no histopathological changes were observed. Group 2 was treated with neomycin sulphate as in group 1, and group 3 was used as control. Blood samples were taken at 8.00 h and 20.00 h daily from both neomycin treated and control horses. Serum creatinine, potassium, sodium and urinary creatinine remained without change. On day...
Marzok M, Almubarak AI, Kandeel M, El-Khodery S.Epidural analgesia using the alpha-2 agonist detomidine (DE), alone or in combination with lidocaine (LD), is frequently employed for standing surgical procedures in horses, but its use has not been evaluated in donkeys. Methods: In a randomised controlled prospective trial, 24 healthy adult donkeys were assigned to four groups (n = 6), each receiving 40 μg/kg of DE, 0.22 mg/kg of LD, combined DE and LD (DELD) or 0.9% sterile normal saline epidurally. After epidural injection of each treatment, the onset, degree and duration of sedation and anatomical extension of anti-nociception were obse...
Beech J, Kohn C, Leitch M, Weinstein AJ, Gallagher M.Serum, synovial fluid, and urine concentrations of gentamicin were measured in normal mature horses which had been given a single dose of the drug. Mean peak serum concentration (16.8 microgram/ml) occurred in horses 30 minutes after they were given a single intramuscular dose of 4.4 mg of gentamicin/kg of body weight. In horses given a smaller dose of gentamicin (1.7 mg/kg), mean peak serum concentrations of gentamicin (10.2 microgram/ml) appeared at 1 hour. Synovial fluid concentration was maximum at 2 hours for both doses; in horses given the larger dose, mean peak concentration was 6.4 mic...
Snow DH, Douglas TA.The absorption characteristics of a new paste preparation of phenylbutazone were studied in ponies and thoroughbreds. The results suggested that at a similar dose rate of 5 mg/kg greater bioavailability results from the paste than from a powder preparation. Delivery of an accurate dosage of the paste was not possible using the multidose applicator. Repeated administration of the paste preparation (5 mg/kg twice daily) indicated that it is more toxic to both ponies and thoroughbreds than a powder preparation. In addition to the toxic manifestations previously reported, a neutropenia developed d...
Hermans H, van den Berg EMH, Slenter IJM, Vendrig DJC, de Nijs-Tjon LJL, Vernooij JCM, Brommer H, Boevé MH, Gehring R.Topical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species. Objective: To investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum. Methods: Prospective randomised experimental pharmacokinetic study. Methods: Twenty-one Shetland ponies without ophthalmic disease...
Craig AM, Blythe LL, Appell LH, Slizeski ML.Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfer...
Rush BR.Pharmacologic manipulation of pulmonary immunity plays an important role in primary and adjunct therapy for equine respiratory disease. Frequent exposure to respiratory viral pathogens, strenuous exercise, long distance transport, and inhalation of harmful substances destroy various aspects of the pulmonary defense system and predispose performance horses to development of infectious and noninfectious respiratory disease. Pulmonary immunity may be bolstered by nonspecific immunostimulants to combat primary or secondary immunodeficiency. State of the art technology improves active and passive-s...
Baggot JD, Love DN, Rose RJ, Raus R.The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (+/- sd) peak serum concentration of 23.2 +/- 10.2 micrograms/ml present at 30 mins, and at 8 h the serum concentration was 2.8 +/- 0.8...
Marr K, Marsh K, Hernandez L, Cunningham FM, Lees P.Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, possess properties consistent with their involvement in a range of inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily) was absorbed from the gastrointestinal tract, and penetrated readily into tissue cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6). Ionophore-stimulated leukotriene (LT) B4 synthes...
Lyons ET, Drudge JH, Tolliver SC.Thirteen critical tests were conducted in horses naturally infected with helminths and bots. Single doses of thiabendazole (44 mg/kg of body weight) and trichlorfon (40 mg/kg of body weight) powder formulations were administered as suspensions sequentially given via stomach tube to evaluate the efficacy of the combination against the large parasites of horses. Parasite removal efficacies were 100% against 2nd instar Gasterophilus intestinalis and 2nd and 3rd instar Gasterophilus nasalis and 82 to 100% against 3rd instar G intestinals. There were complete removals of mature and immature Parasca...
Rauws AG, van Schothorst M, Frik JF.The protein binding, the plasma half-life and the residue depletion of sulfamonomethoxine (SMM) after intramuscular administration were investigated in pigs, horses and cattle. Protein binding was weakly concentration-dependent. The bound fraction in plasma in the therapeutic range amounted to approximately 45, 40 and 50% for pigs, horses and cattle respectively, and the plasma half-lives were approximately 5.1, 5.7 and 3.1 hours respectively. SMM levels were less than 1 mug/g in muscle tissue after 36, 20 and 12 hours in pigs, horses and cattle respectively. In the kidney SMM levels were not ...
Knox DA, Ravis WR, Pedersoli WM, Spano JS, Nostrandt AC, Krista LM, Schumacher J.Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartme...
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...
Fuller CJ, Ghosh P, Barr AR.Results from in vitro studies have indicated that calcium pentosan polysulphate (CaPPS) may be of therapeutic value in osteoarthritis (OA) in the horse. However, no controlled clinical trials using this drug in equine OA have yet been reported. If CaPPS is to be developed for such use, the relationship between the proposed i.m. dose of CaPPS to be used and the concentrations of drug attained in plasma and synovial fluid of the target joint should first be established. An investigation was undertaken to determine these concentrations after a single 2 mg/kg i.m. injection of CaPPS. Blood and syn...
Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK.Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Soma LR, Uboh CE, Guan F, Luo Y, Moate PJ, Boston RC, Driessen B.Hemoglobin-glutamer-200 (HBOC-200) is a hemoglobin (Hb)-based oxygen carrier (HBOC) comprising glutaraldehyde-polymerized bovine Hb. In this study, we sought to determine the pharmacokinetics of this first generation HBOC after IV infusion of 32.5 g of HBOC-200 solution in horses. Quantification of HBOC-200 in equine plasma and urine was performed using a method recently developed by our laboratory. The elimination from plasma was based on size distribution of the bovine Hb polymer. The decline of plasma concentration-time curve of HBOC-200 was described by a noninterchanging 2-compartmental m...
Ortved KF, Goodale MB, Ober C, Maylin GA, Fortier LA.Orthobiologics such as autologous conditioned serum (ACS) are often used to treat joint disease in horses. Because ACS is generated from the horse's own blood, any medication administered at the time of preparation would likely be present in stored ACS, which could lead to an inadvertent positive drug test following intra-articular (IA) injection. The main objective of this study was to determine if ACS prepared from firocoxib positive horses could result in detectable plasma concentrations of the drug following IA injection. Firocoxib was administered to six horses at 0.1mg/kg PO twice at a 2...
Gerken DF, Sams RA.The effects of i.v. chloramphenicol sodium succinate on the pharmacokinetics of i.v. phenylbutazone in six healthy adult horses were investigated. Administration of chloramphenicol sodium succinate to mares reduced mean (+/- SD) phenylbutazone clearance from 0.600 +/- 0.222 to 0.339 +/- 0.123 ml/min per kg and increased mean (+/- SD) half life from 244 +/- 59.8 to 371 +/- 80.8 min and mean residence time from 333 +/- 86.2 to 533 +/- 124 min. The mean steady-state volume of distribution of phenylbutazone was unchanged, with mean (+/- SD) values of 187 +/- 28.9 ml/kg in control animals and 170 +...
Hinchcliff KW, McKeever KH.The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administr...
Sarasola P, McKellar QA.The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
White SD, Maxwell LK, Szabo NJ, Hawkins JL, Kollias-Baker C.To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of i.v. and oral administration of AZA in horses. Methods: 6 horses. Methods: In study phase 1, a single dose of AZA was administered i.v. (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for ...
Checura CM, Momont HW, Castañeira C, Flores-Bragulat A, Losinno L.In horses, prostaglandin E (PGE) is produced by embryos around Day 5 post-ovulation; PGE functions directly at the oviduct promoting embryo transport into the uterus. Non-surgical collection of horse embryos for cryopreservation is recommended at Day 6.5-7 post-ovulation. It was proposed that misoprostol administered orally will hasten oviductal transport of horse embryos. In Experiment 1 (n = 15) there was comparison of time of embryo recovery (Day 6 and 6.5 post-ovulation) from mares administered misoprostol (Day 5 and 5.5) orally to that of untreated mares. On Day 6, embryo collections were...
Velasco-Murillo V.It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug admi...
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...
Stanley SM, Wilhelmi BS, Rodgers JP, Bertschinger H.Immunoaffinity chromatography using a synthesised immunosorbent was used to extract tritiated dexamethasone (with dexamethasone carrier) from equine urine at a recovery of 81.7 +/- 8.4% (mean +/- S.D.). A method utilising this procedure coupled to cool on-column injection gas chromatography-negative ion chemical ionisation mass spectrometry is also described for the confirmation of low levels of flumethasone in equine urine samples.
