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.
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...
Hall TL, Tell LA, Wetzlich SE, McCormick JD, Fowler LW, Pusterla N.Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharma...
Winther L, Baptiste KE, Friis C.Cefquinome concentrations, following intravenous and aerosol administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. Single dose of cefquinome sulphate (1 mg/kg) was administered intravenously to six horses followed by a single aerosol administration (225 mg) with a wash-out period of 14 days between treatments. After each drug administration, cefquinome concentrations in plasma and PELF, obtained by intrabronchial cotton swabs, were determined. After intravenous administration, cefquinome concentrations in plasma declined fast...
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 ...
Natalini CC.In the past 10 years, there have been many recent advances in spinal techniques in horses, both epidural and subarachnoid, to identify drugs or drug combinations that have sensory effects without motor nerve paralysis, thus providing pain control without these horses becoming recumbent. Opioids, alpha-2 agonists, dissociative drugs, and others have been investigated. Many of these drugs, which have serious side effects when injected systemically in horses, have been shown to have useful analgesic effects when injected spinally. Morphine-like opioids have the greatest potential for spinal use a...
van Weeren PR, de Grauw JC.This article focuses on pain associated with osteoarthritis (OA). It first describes the basic biology of articular cartilage and other joint structures and the defining features of the osteoarthritic disease process. Subsequently, the possible origins of pain in OA are discussed before embarking on how to manage this clinical entity. The emphasis is on the pharmacologic management of joint pain, and attention is paid to systemic therapeutic strategies as well as to local (intra-articular) treatment modalities. Nonmedical ways of modulating joint pain are briefly mentioned, but not extensively...
Arnold C, Chaffin MK, Cohen N, Fajt VR, Taylor RJ, Bernstein LR.To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in adult horses. Methods: 6 adult horses. Methods: Feed was withheld for 12 hours prior to intragastric administration of GaM (20 mg/kg). A single dose of GaM was administered to each horse via a nasogastric tube (time 0). Blood samples were collected at various time points from 0 to 120 hours. Serum was used to determine gallium concentrations by use of inductively coupled plasma-mass spectroscopy. Noncompartmental and compartmental analyses of serum gallium concentrations were performed. Pharmacoki...
Giorgi M, Cuniberti B, Ye G, Barbero R, Sgorbini M, Vercelli C, Corazza M, Re G.Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasm...
Scarth JP, Teale P, Kuuranne T.A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism...
Gehring R, Beard L, Wright A, Coetzee J, Havel J, Apley M.Pituitary pars intermedia dysfunction (PPID) is probably the most common disease of geriatric horses. Affected horses show a variety of clinical signs, including hirsutism, polyuria/polydipsia, immunosuppression, muscle wasting, and laminitis. The most common treatment for PPID is pergolide, a dopamine agonist; however, there are no pharmacokinetic data about the use of this drug in horses. This article describes a study designed to address this complete lack of pharmacokinetic information. The pharmacokinetics of pergolide are described in a small group of relatively young, healthy mares (n =...
Yu J, Han KS, Lee G, Paik MJ, Kim KR.The enantioseparation of pranoprofen after its addition in racemic form into equine plasma and urine was conducted by chiral liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. The methods for the assay of both enantiomers were linear (r≥0.9943) in the low range from 0.001 to 0.1μg/mL and high range from 0.01 to 1.0μg/mL with good precision (% RSD≤5.6) and accuracy (% RE=-5.3 to 1.9). When racemic pranoprofen was orally administered to four horses at a single dose of 3.1mg/kg, the median plasma concentrations of (R)-pranoprofen were lower than the levels ...
Becher AM, Pfister K.In recent years more and more cases of anthelmintic resistant equine strongyles were reported. The latest developments are cases of resistance against macrocyclic lactones. In order to delay this process less anthelmintics and only those which have been previously tested for their efficacy on each individual farm should be used. During the grazing season 2008 faecal samples of 281 horses and 5 donkeys from 26 farms were analysed in the area of Salzburg. To 164 of these horses selective anthelmintic treatment was implemented. Every four weeks faecal samples from the 164 horses were quantitative...
Tinworth KD, Edwards S, Noble GK, Harris PA, Sillence MN, Hackett LP.To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies. Methods: 8 IR ponies. Methods: Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 d...
Scarth JP, Spencer HA, Timbers SE, Hudson SC, Hillyer LL.The detection of drug abuse in horseracing often requires knowledge of drug metabolism, especially if urine is the matrix of choice. In this study, equine liver/lung microsomes/S9 tissue fractions were used to study the phase I metabolism of eight drugs of relevance to equine drug surveillance (acepromazine, azaperone, celecoxib, fentanyl, fluphenazine, mepivacaine, methylphenidate and tripelennamine). In vitro samples were analyzed qualitatively alongside samples originating from in vivo administrations using LC-MS on a high resolution accurate mass Thermo Orbitrap Discovery instrument and by...
Li XQ, Uboh CE, Soma LR, Guan FY, You YW, Kahler MC, Judy JA, Liu Y, Chen JW.A non-aqueous capillary electrophoresis-mass spectrometry (NACE-MS) method was developed for simultaneous separation and identification of 12 amphetamine and related compounds in equine plasma. Analytes were recovered from plasma by liquid-liquid extraction using methyl tertiary butyl ether (MTBE). A bare fused-silica capillary was used for separation of the analytes. Addition of sheath liquid to the capillary effluent allowed the detection of the analytes by positive electrospray ionization mass spectrometry using full scan data acquisition. The limit of detection (LOD) for the target analyte...
Levine DG, Epstein KL, Ahern BJ, Richardson DW.To determine (1) if clinically useful concentrations of amikacin sulfate can be obtained in synovial fluid during regional limb perfusion (RLP) performed above the carpus in standing sedated horses and (2) to determine the efficacy of 3 tourniquet types (narrow rubber [NR], wide rubber [WR], pneumatic [PN]). Methods: Horses (n=9). Methods: Bilateral forelimb RLP with amikacin sulfate (2.5 g) were administered through the cephalic vein in standing sedated horses. Limbs were randomly assigned to the 3 tourniquet types (NR, WR, PN) applied above the carpus. Metacarpophalangeal synovial fluid was ...
Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B.Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gaba...
Dimaio Knych HK, Steffey EP, Stanley SD.Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered a...
Nagata S, Yamashita S, Kurosawa M, Kuwajima M, Hobo S, Katayama Y, Anzai T.To determine the pharmacokinetics and tissue distribution of minocycline in horses. Methods: 5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment. Methods: Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study. Results: No adverse effects were observed in any of the ...
Winther L, Guardabassi L, Baptiste KE, Friis C.Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Add...
Winther L, Honoré Hansen S, Baptiste KE, Friis C.Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for do...
Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D.No studies have determined the pharmacokinetics of low-dose amikacin in the mature horse. Objective: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n=6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n=6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean±s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time ze...
Rezende ML, Boscan P, Stanley SD, Mama KR, Steffey EP.To characterize cardiovascular, respiratory and biochemical effects and recovery behavior associated with a 3-hour continuous infusion of a micellar microemulsion propofol formulation in horses. Methods: Prospective experimental trial. Methods: Six healthy adult horses, 9 +/- 2 years old and weighing 557 +/- 14 kg. Methods: All horses received xylazine (1 mg kg(-1), IV) 5 minutes prior to anesthetic induction. Each horse was anesthetized on two occasions with a 5% micellar microemulsion propofol formulation (2 mg kg(-1), IV); first as a single bolus (phase I) and then as a 3-hour continuous in...
Kornreich B, Enyeart M, Jesty SA, Nydam DV, Divers T.Pentoxifylline (PTX) possesses a number of vasomotor, immunomodulatory, and hemorheologic properties. Based upon the hypothesis that equine laminitis and navicular disease result from microthrombosis, the inhibitory effects of PTX on inflammatory cytokines, and its inhibitory effects on human platelet aggregation, PTX has been widely used to treat equine endotoxemia, navicular disease, and laminitis. Despite this, the effects of PTX on equine platelet aggregation have not been investigated previously. Objective: PTX decreases platelet aggregation in equine whole blood at concentrations approxi...
Mathes RL, Reber AJ, Hurley DJ, Dietrich UM.To evaluate the effects of topical antifungal drugs and delivery vehicles on the morphology and proliferation rate of cultured equine keratocytes. Methods: 16 corneas obtained from 8 apparently ophthalmologically normal horses < 0.5 hours after euthanasia for reasons unrelated to the study. Methods: Primary cultures of equine keratocytes were obtained from corneal stroma and were exposed to several concentrations of 3 commonly used, topically applied antifungals: natamycin, itraconazole, and miconazole. In addition, effects of drug delivery vehicles DMSO, benzalkonium chloride, and carboxym...
Armengou L, Monreal L, Delgado MÁ, Ríos J, Cesarini C, Jose-Cunilleras E.Heparin is used in humans as prophylaxis of hypercoagulable states and disseminated intravascular coagulation (DIC). However, babies need a higher heparin dose than do adults. Septic neonate foals are at high risk of hypercoagulable state and DIC, and there is limited objective information about heparin dose for equine neonates. Objective: To assess whether neonate foals require higher dosages of low-molecular-weight heparin (LMWH) than adults. Methods: Eighteen healthy and 11 septic neonate foals. Methods: Experimental and clinical studies. Firstly, healthy foals were randomly distributed in ...
Kim I, Cohen ND, Roussel A, Wang N.Gastric emptying studies are of great interest in human and veterinary medical research to evaluate effects of medications or diets for promoting gastrointestinal motility and to examine unintended side-effects of new or existing medications, diets, or procedures. Summarizing gastric emptying data is important to allow easier comparison between treatments or groups of subjects and comparisons of results among studies. The standard method for assessing gastric emptying is by using scintigraphy and summarizing the nonlinear emptying of the radioisotope. A popular model for fitting gastric emptyi...
Chaffin MK, Fajt V, Martens RJ, Arnold CE, Cohen ND, O'Conor M, Taylor RJ, Bernstein LR.Gallium is a trivalent semi-metal with anti-microbial effects because of its incorporation into crucial iron-dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM-MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and ...
Nostrandt AC, Pedersoli WM, Marshall AE, Ravis WR, Robertson BT.Ototoxicosis was evaluated in 6 healthy ponies given 5 mg of gentamicin/kg of body weight, q 8 h, IM. Ponies 1, 2, and 3 were dosed for 7 days and ponies 4, 5, and 6 were dosed for 14 days. Serum peak and trough concentrations of gentamicin were measured by radioimmunoassay at regular intervals. Brain stem auditory-evoked responses were recorded every 5 days up to 60 days after the first dose to monitor auditory function. Although serum gentamicin concentrations were within or above the accepted clinical therapeutic range, loss of auditory function was not observed at the frequency range (1 to...
Lyons ET, Drudge JH, Tolliver SC, Swerczek TW, Collins SS.A total of 59 equids (54 horses and five Shetland ponies) were treated with pyrantel pamoate once, at the dose rate of approximately 6.6 mg base kg-1, during the period November 1985-January 1988. The drug was administered as a paste formulation (51 equids) intraorally or as a suspension formulation by stomach tube (eight equids). The purpose of treatment was to evaluate the activity of pyrantel pamoate (at the therapeutic dose rate) for removal of the tapeworm, Anoplocephala perfoliata, by a modified (24-h) critical test. The presence or absence of tapeworms was not determined for the equids ...
Haerdi-Landerer MC, Habermacher J, Wenger B, Suter MM, Steiner A.The search for an effective treatment for septic arthritis is ongoing. Current therapies are expensive since they require repeated joint lavage and long term antibiotic treatment. Local application of antimicrobial drugs is advantageous because high concentrations can be attained at the infection site, although repeated injections increase the risk of superinfection of the joint. Thus, slow release formulations, which have the advantage of local treatment yet single application of the drug, are appealing. Antibiotics used in slow release formulations are selected for tissue compatibility, an a...
Johansson AM, Gardner SY, Levine JF, Papich MG, LaFevers DH, Fuquay LR, Reagan VH, Atkins CE.Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically signific...
Palm FM, Schenk I, Neuhauser S, Schubert D, Machnik M, Schänzer W, Aurich C.Treatment with the progestin altrenogest is widely used in pregnant mares. The fact that foals born from healthy mares treated with altrenogest until term suffered from neonatal problems raises the question of direct effects of altrenogest on vital functions in the neonate. We have therefore investigated altrenogest concentrations in maternal and neonatal blood plasma and in fetal fluids. Pregnant mares were treated with altrenogest orally once daily (0,088 mg/kg bodyweight, n = 7) or left untreated (n = 8) from 280 d of gestation until foaling. Altrenogest concentration was determined in plas...
Mück WM, Henion JD.A screening procedure for the anabolic steroid stanozolol in human and equine urine was developed based on enzymatic hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography combined on-line with tandem mass spectrometry. The column effluent was introduced into the atmospheric pressure ionization source of a triple-quadrupole mass spectrometer via a heated pneumatic nebulizer liquid chromatograph/mass spectrometer interface. Abundant protonated molecular ions were generated by corona discharge ionization. Confirmation of stanozolol and several of its hydroxylated and dihyd...
Wilson CR, Sauer JM, Carlson GP, Wallin R, Ward MP, Hooser SB.A comparative study of vitamin K(1) 2,3-epoxide reductase (VKOR) activity in vitro was conducted across species. The apparent kinetic constants K(m app), V(max), and Cl(int app) were determined in bovine, canine, equine, human, murine, ovine, porcine, and rat hepatic microsomes. In addition to these enzyme kinetic constants, the IC(50) of warfarin for VKOR was determined in human, murine, porcine, and rat hepatic microsomes. Interspecies differences were observed when comparing the K(m app) (range, 2.41-6.46 microM), V(max) (range, 19.5-85.7 nmol/mg/min), and Cl(int app) (range, 8.2-18.4 ml/mg...
Carmichael RJ, Whitfield C, Maxwell LK.Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV-1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV-1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross-over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenousl...
Sweeney RW, Divers TJ, Rossier Y.Plasma concentration of gentamicin was measured 1, 4, and 6 hours after IV administration in 35 hospitalized adult horses on days 1, 3, 5, and 10 of treatment. The mean apparent elimination rate constant beta was 0.53 +/- 0.10 h-1 on day 1 for horses with normal plasma creatinine concentration and 0.41 +/- 0.13 h-1 for horses with abnormally high plasma creatinine concentration. There was no significant difference between beta of the hospitalized horses and of 6 healthy horses treated with gentamicin, but total clearance for the hospitalized horses with normal plasma creatinine concentration w...
Bettembourg V, Dulgheriu D, Haga HA.To determine dexmedetomidine plasma concentrations at two infusion rates in isoflurane anaesthetized horses and compare cardiovascular effects and anaesthetic recovery between treatments. Methods: Prospective, randomized, masked clinical study. Methods: Healthy, adult, client-owned, non-food producing horses presented for castration. Methods: Premedication consisted of acepromazine, romifidine and morphine, and anaesthesia was induced with ketamine and midazolam. The horses were randomized to receive dexmedetomidine 0.5 μg kg hour (treatment DL, n = 7) or 1.75 μg kg hour (treatment DH, n =...
Knych HK, Stanley SD, McKemie DS, Arthur RM, Kass PH.There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24 hours. The primary goal of the study reported here was to update the pharmacokinetics of xylazine following intravenous (IV) administration in order to assess the applicability of current regulatory recommendations. Pharmacodynamic parameters were determined using PK-PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96 hours and analyzed...
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....
Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH.The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercis...
Leung GN, Leung DK, Wan TS, Wong CH.This paper describes a high throughput LC-MS-MS method for the screening of 75 basic drugs in equine plasma at sub-ppb levels. The test scope covers diversified classes of drugs including some alpha- and beta-blockers, alpha- and beta-agonists, antihypotensives, antihypertensives, analgesics, antiarrhythmics, antidepressants, antidiabetics, antipsychotics, antiulcers, anxiolytics, bronchodilators, CNS stimulants, decongestants, sedatives, tranquilizers and vasodilators. A plasma sample was first deproteinated by addition of trichloroacetic acid. Basic drugs were then extracted by solid-phase e...
Ho EN, Kwok WH, Wong AS, Wan TS.A recent trend in the use of high resolution accurate mass screening (HRAMS) for doping control testing in both human and animal sports has emerged due to significant improvement in high resolution mass spectrometry in terms of sensitivity, mass accuracy, mass resolution, and mass stability. A number of HRAMS methods have been reported for the detection of multi-drug residues in human or equine urine. As blood has become a common matrix for doping control analysis, especially in equine sports, a sensitive, fast and wide coverage screening method for detecting a large number of drugs in equine ...
Harkins JD, Mundy GD, Woods WE, Lehner A, Karpiesiuk W, Rees WA, Dirikolu L, Bass S, Carter WG, Boyles J, Tobin T.Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration...
Katzman SA, Cissell D, Leale D, Perez-Nogues M, Hall MD, Bloom G, Hamamoto-Hardman B, Wu CY, Haudenschild AK, Liu GY, Yik JHN, Haudenschild DR.To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. Methods: 4 healthy horses without evidence of forelimb lameness. Methods: A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral ...
Sergazy S, Zhetkenev S, Shulgau Z, Chulenbayeva L, Kamyshanskiy Y, Nurgaziyev M, Nurgozhina A, Mukhanbetzhanova Z, Berikkhanova K, Gulyayev A....Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare's milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare's milk-derived exosomes as potential therapeutic carriers. Three extraction methods-immunoprecipitation, size exclusion ch...
Robertson SA.The alleviation of pain in foals is an important welfare issue, increases patient and personnel safety, results in less disruption of homeostasis, and enhances return to normal function. It is important to anticipate and prevent noxious stimuli because pain in the neonatal period can alter pain processing, leading to altered pain thresholds and responses later in life as well as aversive behaviors. The key to assessing pain in foals is observation of behavior. Despite limited pharmacokinetic and efficacy information, understanding the unique physiology of foals and the mode of action of availa...
Schatzmann U, Tschudi P, Held JP, Muhlebach B.Glyceryl guaiacolate (GGE) was found to be a useful and safe casting agent when given by rapid intravenous infusion. It was administered to premedicated horses under controlled conditions at various concentrations from 10 to 20 per cent GGE solution. The onset and degree of relaxation was dependent only on the speed of infusion. For casting adult horses 350 to 450 ml of 15 per cent solution must be given within 30 to 60 seconds. A slight transient hypoxaemia occurred which seemed to be related to the animal being in lateral recumbency rather than the depressive action of GGE on respiratory fun...
Reed R, Trenholme N, Skrzypczak H, Chang K, Ishikawa Y, Barletta M, Quandt J, Knych H, Sakai D.To compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses. Methods: Randomized controlled clinical trial. Methods: A total of 40 adult horses admitted for elective arthroscopy. Methods: Horses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg-1; group TxH; n = 19) or butorphanol (0.02 mg kg-1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht...
Nannarone S, Gialletti R, Veschini I, Bufalari A, Moriconi F.Alpha-2 agonists are synthetic drugs which cause sedation, analgesia and myorelaxation due to their interaction with alpha-2 adrenoreceptors, widely distributed throughout bodily systems. Because of these actions such drugs are generally used in veterinary practice: to tranquilize animals (pharmacologic restraint) for the safety of both veterinar-ians and cooperators. Such properties facilitate diagnostic examinations or minimally in-vasive and poorly painful surgical procedures, as well as limiting stress factors to the patients. The aim of this study is to find out the minor dosage able to m...
Sweeney RW, Beech J, Simmons RD.Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After in...
Yamanaka T, Yamada M, Tsujimura K, Kondo T, Nagata S, Hobo S, Kurosawa M, Matsumura T.The aim of this study was to investigate the pharmacokinetics of oseltamivir carboxylate (OC) in horses (n=6) after oral administration of its prodrug oseltamivir. The binding rate of OC to horse plasma proteins was negligible (<1%). Oral administration of oseltamivir of 2 mg/kg body weight of oseltamivir to horses provided a plasma concentration of OC (mean maximum concentration: 257.9 ng/ml) above the inhibitory concentrations against equine influenza A viruses determined in vitro. However, because OC is rapidly eliminated from horse plasma (mean elimination half-life: 2.5 hr), administratio...
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...
Sams RA.This article is intended to give the reader an understanding of the mathematic and conceptual framework underlying equine pharmacology. The methods by which the veterinary practitioner determines drug concentrations, disposition, and bioavailability are discussed.
Brown MP, Embertson RM, Gronwall RR, Beal C, Mayhew IG, Curry SH.Six mares were given 5 IM injections (at 12-hour intervals between doses) of amikacin sulfate at a dosage of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially throughout the study; synovial, peritoneal, endometrial, and urine concentrations were determined after the last injection. Amikacin concentrations of the CSF were measured serially in 3 of the 6 mares; 1 of the 3 mares had septic meningitis. Mean serum amikacin concentrations peaked at 1 to 2 hours after IM injection. The highest mean serum concentration was 19.2 micrograms/ml (1.5 hours after the 5th injectio...
