The topic of drugs and horses encompasses the study of various pharmacological agents used in equine medicine for therapeutic purposes. This includes the administration of medications for pain management, disease treatment, and performance enhancement. The pharmacokinetics and pharmacodynamics of drugs in horses are key areas of research, as they determine the absorption, distribution, metabolism, and excretion of these substances. Additionally, the topic covers the detection and regulation of substances in competitive equestrian sports to ensure fair play and animal welfare. This page compiles peer-reviewed research studies and scholarly articles that explore the effects, safety, and regulatory aspects of drug use in equine health and performance.
Stanley SM.The metabolism and urinary excretion of a 100 mg dose of the non-sedating anxiolytic drug buspirone was examined using high-performance liquid chromatography/electrospray ionization mass spectrometry in the positive ion mode. In addition to a significant proportion of unchanged buspirone we were able to detect three major metabolite classes. These were identified as monohydroxy, dihydroxy and dihydroxymethoxy products. Detection of the metabolites and the parent drug was possible in all the urine samples collected (1-12 h) post-administration.
Furr M, Kennedy T.Toltrazuril 5% suspension (Baycox, Bayer Canada, Ontario, Canada) was administered to six adult horses followed by blood collection and assay to determine the concentration of toltrazuril and its principal metabolites, toltrazuril sulfone and toltrazuril sulfoxide. From this data, the maximum concentration (C(max)), elimination half-life (T 1/2), and mean residence times of the plasma were determined from standard pharmacokinetic formulas. After a single oral dose of 10 mg/kg body weight a rapid absorption was found, with a mean peak serum concentration of 11.17 mg/L at 18 hours. Elimination w...
Törneke K, Larsson CI, Appelgren LE.Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H-isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The K(d) values were 0.02 mmol/l and 1 mmol/l, and the B(max) values were 0.2 micromol/mg and 2 micromol/mg, respectively. A ...
Belloli C, Carcano R, Arioli F, Beretta C.We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsup...
Bennett-Wimbush K, Loch WE, Plata-Madrid H, Evans T.Nineteen anestrous pony mares were used in a project designed to determine the effects of altered prolactin concentrations on follicular dynamics and endocrine profiles during spring transition. The dopamine antagonist, perphenazine, was administered daily to mares (0.375 mg/kg body weight) in Group A (n = 6), while Group B mares (n = 7) received 0.08 mg/kg metabolic weight (kg75) dopamine agonist, 2-bromo-ergocriptine, intramuscularly twice daily. Mares in Group C (n = 6) received 0.08 mg/kg75, i.m., saline twice daily. Treatment began January 20, 1994, and continued until ovulation occurred....
Sasaki N, Yoshihara T.Seven Thoroughbred horses were laparotomized and Force Transducers were fixed on the proximal jejunal and cecal serosa. After observation of the digestive tract motility in consciousness, cisapride (0, 0.5, 0.75 or 1 mg/kg) was orally administered. In horses treated with 0.75 mg/kg or 1.0 mg/kg cisapride, the migrating contraction (MC) of the jejunum was significantly increased in frequency.
Wierdl M, Morton CL, Danks MK, Potter PM.Butyrylcholinesterases (BuChEs; acylcholine acylhydrolase; EC 3.1.1.8) have been demonstrated to convert the anticancer agent CPT-11 (irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) into its active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin). In addition, significant differences in the extent of drug metabolism have been observed with BuChEs derived from different species. In an attempt to understand these differences, we have isolated the cDNA encoding a horse BuChE. Based upon the NH2-terminal amino acid sequence of a purified horse BuChE, we designed deg...
The Journal of parasitologyMarch 4, 2000
Volume 86, Issue 1 164-166 doi: 10.1645/0022-3395(2000)086[0164:DOTAOD]2.0.CO;2
Lindsay DS, Dubey JP.Diclazuril is a benzeneacetonitril anticoccidial that has excellent activity against the extraintestinal stages of Toxoplasma gondii and Neospora caninum. It also is highly active against intestinal coccidia of poultry. The present study examined the efficacy of diclazuril in inhibiting merozoite production of Sarcocystis neurona and Sarcocystis falcatula in bovine turbinate cell cultures. Diclazuril inhibited merozoite production by more than 80% in cultures of S. neurona or S. falcatula treated with 0.1 ng/ml diclazuril and greater than 95% inhibition of merozoite production was observed whe...
Murray MJ, Eichorn ES, Holste JE, Cox JL, Stanier WB, Cooper WL, Cooper VA.A paste formulation of the H+,K(+)-ATPase inhibitor omeprazole was evaluated in Thoroughbred foals and yearlings for its safety and acceptability. Twenty foals age 11-16 weeks and 20 yearling horses age 15-17 months were included and gastroscopic examinations performed 1-3 days before and at the end of each trial. Lesions were scored on a scale of 0 to 3 and animals allocated based on endoscopic lesion score and sex, with 4 animals in each of 5 replicates. Dosages of 4 mg omeprazole/kg bwt or sham treatment were administered once daily for 28 days, from a syringe graduated in 50 lb (22.68 kg) ...
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...
Raisis AL, Young LE, Meire HB, Taylor PM, Blissitt KJ, Marlin D, Lekeux P.The purpose of the study was to determine the ability of Doppler ultrasound to detect changes in femoral blood flow during pharmacologic manipulation of arterial blood pressure. Doppler ultrasonography was performed in the femoral vessels of six halothane-anesthetized horses before and during administration of phenylephrine HCI and sodium nitroprusside. The time-averaged mean velocity and volumetric flow were calculated. The contour of the velocity waveform was assessed, and the early diastolic deceleration slope (EDDS) and pulsatility index (PI) were calculated. Administration of phenylephrin...
Cogley TP, Cogley MC.A synthetic alpha-2 adrenergic agonist, detomidine hydrochloride, was used in the study of in vivo activity of Gasterophilus intestinalis (Diptera: Gasterophilidae) during migration in the tongue of the horse. Use of the drug allowed the investigator to manipulate the tongue and closely observe the movement patterns and tissue disturbance caused by burrowing first-stage larvae. Detomidine hydrochloride should be utilized in studies of drug efficacy and larval biology, whenever possible, to avoid the need to sacrifice the horse.
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 ...
Suominen MM, Tulamo RM, Puupponen LM, Sankari SM.To evaluate effects of intra-articular (i.a.) injections of bufexamac on amphotericin B-induced aseptic arthritis in horses. Methods: 24 Standardbred horses. Methods: Aseptic arthritis was induced in the right intercarpal joint by i.a. injection of amphotericin B (20 mg). One week later (day 0), horses were randomly assigned to four 6-horse treatment groups and treated with i.a. injection of 10, 20, or 40 mg of bufexamac suspension (20 mg/ml) or 2.0 ml of sterile saline (0.9% NaCl) solution (control). The treatment was repeated once after 7 days. Clinical lameness examinations and synovial flu...
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...
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.
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...
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...
Bueno AC, Cornick-Seahorn J, Seahorn TL, Hosgood G, Moore RM.To determine the cardiopulmonary and sedative effects of medetomidine hydrochloride in adult horses and to compare those effects with effects of an equipotent dose of xylazine hydrochloride. Methods: 10 healthy adult female horses. Methods: 5 horses were given medetomidine (4 microg/kg of body weight, i.v.), and the other 5 were given xylazine (0.4 mg/kg, i.v.). Heart rate, respiratory rate, arterial blood pressures, pulmonary arterial blood pressures, and cardiac output were recorded, and sedation and ataxia scores were assigned before and every 5 minutes after drug administration for 60 minu...
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...
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...
Sangster NC.Anthelmintic-resistance has emerged as a problem in several animal industries. In the horse, cyathostome resistance to all available treatments except for the avermectin/milbemycins means that these drugs provide the cornerstone of control. Ivermectin has been available for several years; the related compound moxidectin is more recent. Although we do not know for sure, aspects of moxidectin such as its persistent action and its efficacy against mucosal stages of cyathostomes, may enhance the rate of development of resistance. On the other hand, selection pressure would be reduced if the persis...
Gadaj A, Ventura E, Healy J, Botrè F, Sterk SS, Buckley T, Mooney MH.Selective androgen receptor modulators (SARMs) represent non-steroidal agents commonly abused in human and animal (i.e. equine, canine) sports, with potential for further misuse as growth promoting agents in livestock-based farming. As a direct response to the real and possible implications of illicit application in both sport as well as food production systems, this study incorporated enzymatic hydrolysis (β-glucuronidase/arylsulfatase) into a previously established protocol while maintaining the minimal volume (200 µL) of urine sample required to detect SARMs encompassing various pharmacop...
Dirikolu L, Karpiesiuk W, Lehner AF, Tobin T.Toltrazuril sulfone (ponazuril) is a triazine-based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400 ± 169 (SEM) ng/mL occurring at 8 h after oral-mucosal dosing and was about 56% bioavailable compared with the i.v. administration of toltrazuril sul...
Bailly-Chouriberry L, Cormant F, Garcia P, Kind A, Popot MA, Bonnaire Y.Cobra venom (Naja kaouthia) contains a toxin called α-cobratoxin (α-Cbtx). This toxin is a natural protein containing 71 amino acids (MW 7821 Da) with a reported analgesic potency greater than morphine. In 2007, in USA, this substance was found in the barns of a thoroughbred trainer and since then till date, the lack of a detection of this molecule has remained a recurring problem for the horseracing industry worldwide. To solve this problem, the first method for the detection of α-cobratoxin in equine plasma has now been developed. Plasma sample (3 mL) was treated with ammonium sulfate at ...
Lyons ET, Drudge JH, Tolliver SC, Swerczek TW, Stamper S, Granstrom DE.Studies in a band of ponies harboring Population S benzimidazole-resistant small strongyles were initiated in 1974 and have continued for 18 years. Treatment (bimonthly) was with cambendazole for the first 4 years and with oxibendazole (OBZ) for the next 14 years. Data on the first 10 years have been published. The present investigation includes the last 8 years (4 October 1984-11 September 1992), which are the seventh through fourteenth years, of treatment with OBZ. Pre- and posttreatment mean counts of strongyle eggs (epg) and larvae (lpg) per gram of feces were determined biweekly during th...
Kwok WH, Leung DK, Leung GN, Wan TS, Wong CH, Wong JK.A rapid liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for the simultaneous screening of 19 drugs of different classes in equine plasma using automated on-line solid-phase extraction (SPE) coupled with a triple quadrupole mass spectrometer. Plasma samples were first protein precipitated using acetonitrile. After centrifugation, the supernatant was directly injected into the on-line SPE system and analysed by a triple quadrupole LC-MS-MS in positive electrospray ionisation (+ESI) mode with selected reaction monitoring (SRM) scan function. On-line extraction and c...
Gozalo-Marcilla M, Hopster K, Gasthuys F, Krajewski AE, Schwarz A, Schauvliege S.To compare the effects of a constant rate infusion (CRI) of dexmedetomidine and morphine to those of morphine alone on the minimum end-tidal sevoflurane concentration necessary to prevent movement (MACNM ) in ponies. Methods: Prospective, randomized, crossover, 'blinded', experimental study. Methods: Five healthy adult gelding ponies were anaesthetized twice with a 3-week washout period. Methods: After induction of anaesthesia with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (Fe'SEVO 2.5%) i...
Ingvast-Larsson C, Paalzow G, Paalzow L, Ottosson T, Lindholm A, Appelgren LE.The pharmacokinetics of theophylline were determined in Standardbred trotters after single intravenous and oral administration. A bi-exponential equation was fitted to the intravenous data and a tri-exponential equation to the oral data. The biological half-life of theophylline was found to be 14.8 h, the volume of distribution 1.02 l/kg and the total plasma clearance 0.86 ml/kg/min. The oral absorption of the drug was complete (bioavailability 108%) and rapid (absorption half-life 0.4 h).
Boone LH, DeGraves FJ, Klein CE, Cole RC, Schumacher J.To assess onset of analgesia for 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when used for median and ulnar nerve blocks in lame horses. Methods: 6 naturally lame horses. Methods: A crossover experiment was conducted. Horses were assigned to 1 of 2 treatment groups (3% chloroprocaine or 2% mepivacaine first). Median and ulnar nerve blocks were performed in the lame limb with the assigned treatment. Lameness was objectively evaluated before treatment administration and at various points for 120 minutes after treatment with a wireless inertial sensor-based motion analysis sy...
Houghton E, Dumasia MC, Wellby JK.Negative ion chemical ionization mass spectra of some corticosteroids have been obtained by direct syringe introduction on to the Finnigan moving belt high-performance liquid chromatography-mass spectrometer interface. Proprietary preparations based upon dexamethasone, betamethasone and prednisolone were administered to horses at therapeutic dose level. Urine samples were extracted, the extracts purified by Sephadex LH-20 chromatography and the presence of the parent steroids in the eluates was confirmed by combined high-performance liquid chromatography negative ion chemical ionization mass s...
Johnson E, van Heemst J, Benavides J, Gray B.Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India but has recently appeared as a nonapproved product on the illicit drug market in Europe and North America. Etizolam was identified in a crystalline material seized at a Kentucky racetrack, raising concerns that this drug may have been used in racing. The aim of this study was to characterize the metabolism and excretion of etizolam in horses to generate information on its disposition and to incorporate the correct urinary and serum target analytes into anti-doping screening procedures. Etizolam was adminis...
Hilton HG, Magdesian KG, Groth AD, Knych H, Stanley SD, Hollingsworth SR.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. Objective: To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. Methods: Fifteen healthy adult horses with no evidence of ophthalmic disease. Methods: Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups rece...
Berlin S, Wallstabe S, Scheuch E, Oswald S, Hasan M, Wegner D, Grube M, Venner M, Ullrich A, Siegmund W.Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. Objective: To evaluate the pharmacokinetic ...
Oehme FW.Animals are constantly exposed to a wide variety of foreign chemicals, many of which are potentially toxic and some of which result in the clinical poisonings. Pesticides are applied on or around animals for the control of insects and rodents. These chemicals may be placed in areas without regard for accessibility to household pets and domestic livestock. Insecticides, herbicides, and fungicides are routinely and haphazardly applied to animal and environmental surfaces alike with apparent disregard for differences in absorptive capability. Fortunately, newer herbicides and fungicides are relat...
Willette C, Aarnes TK, Lerche P, Ricco-Pereira C, Ballash GA, Bednarski RM.To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. Methods: Randomized, blinded, three-way crossover prospective design. Methods: A total of eight healthy adult horses weighing 470-575 kg. Methods: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg), ketamine (1 mg kg) and detomidine (0.04 mg kg) (treatment TKD); ketamine (3 mg kg) and detomidine (0.04 mg kg) (treatment KD); and tiletamine-zolazepam (2.4 mg ...
Koupai-Abyazani MR, Esaw B, Laviolette B.Urine and serum samples collected from four standard-bred mares after and oral regimen administration of methocarbamol were extracted and analyzed. The method consisted of enzyme hydrolysis followed by a one-step liquid-liquid extraction, separation on a reversed-phase (RP-18) column, and detection using an ultraviolet (UV) detector. The confirmation was carried out using a liquid chromatography-atmospheric pressure ionization-mass spectrometry (LC-API-MS) system. Maximum methocarbamol concentrations of 1498, 1734, 1547, 2322 micrograms/mL in urine and 4.9, 1.7, and 3.6 micrograms/mL in serum ...
Otten N, Marti E, Söderström C, Amtmann E, Burger D, Gerber H, Lazary S.A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to...
Duesterdieck-Zellmer KF, Moneta L, Ott JF, Larson MK, Gorman EM, Hunter B, Löhr CV, Payton ME, Morré JT, Maier CS.To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggr...
Stanley SM, Wee WK, Lim BH, Foo HC.Direct-injection LC-LC hybrid tandem MS methods have been developed for undertaking broad-based screening for acidic drugs in protein-precipitated plasma and neutral doping agents in equine urine. In both analyses, analytes present in the matrix were trapped using a HLB extraction column before being refocused and separated on a Chromolith RP-18e monolithic analytical column using a controlled differential gradient generated by proportional dilution of the first column's eluent with water. Each method has been optimised by the adoption of a mobile phase and gradient that was tailored to enhanc...
Roska S, Morello S, Rajamanickam V, Smith LJ.Effects of lactated Ringer's solution (LRS) and hetastarch 130/0.4 (HES) on colloid osmotic pressure (COP), plasma osmolality (OSM) and total protein (TP) were investigated in 18 inhalational-anaesthetised healthy horses. Horses received 4-6 ml/kg LRS (LRS; n=9) or HES (HES; n=9) from anaesthesia induction through 60 min, after which all were administered LRS. COP, TP and OSM were measured before premedication (baseline), postinduction and 30 (n=18), 60 (n=18), 90 (n=18) and 120 (n=12) minutes. Baseline COP, OSM and TP were not different between groups. TP decreased in both groups at all t...
Liu Y, Uboh CE, Soma LR, Li X, Guan F, You Y, Rudy JA, Chen JW.In 2008, Pennsylvania (PA) became the first State in the USA to ban and enforce the ban on the use of anabolic and androgenic steroids (AAS) in equine athletes by using plasma for analysis. To enforce the ban, a rapid and high-throughput method for analysis of 60 AAS in equine plasma was developed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analytes were recovered from plasma by liquid-liquid extraction (LLE) using methyl tert-butyl ether, separated on a reversed-phase C₁₈ column and analyzed by electrospray ionization mass spectrometry. Multiple-reaction monitoring (MRM)...
Igwe OJ, Blake JW.The disposition kinetics of pemoline after iv and oral administration of 2.4 mg/kg of the drug were studied. The elimination half-life was 39.4 hr. The mean volume of distribution was 1.5 liters/kg indicating extensive tissue distribution and sequestration for an amphoteric drug. Plasma protein binding determined by in vitro equilibrium dialysis was concentration dependent. The mean binding capacity was found to be 0.80 mu-mol/g, an apparent dissociation constant of 3.73 X 10(-5) molar, and a total plasma protein concentration of 64.7 g/liter. The mean systemic availability by oral administrat...
Uboh CE, Rudy JA, Railing FA, Enright JM, Shoemaker JM, Kahler MC, Shellenberger JM, Kemecsei Z, Das DN.Although urine is the sample of choice for drug tests in racehorses, it is rarely obtained following the sudden death of a racehorse on the track while racing. The purpose of this study was to demonstrate the significance of postmortem tissue samples as an alternative to urine and blood samples in equine drug analysis following the sudden death of a racehorse on the track while participating in a competitive race. Postmortem tissue samples were frozen (-80 degrees C) until analyzed. A 30-40-g portion of each organ was homogenized in a 0.1 M phosphate buffer (pH 7.4), deproteinized, hydrolyzed ...
Singh S, Young SS, McDonell WN, O'Grady M.Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV a...
Barker SA.Advances in analytical technology now make it feasible to detect and confirm exceptionally low concentrations (pg to fg/mL) of drugs and their metabolites in equine biological fluids. These new capabilities complicate the regulatory interpretation of drug positives and bring into question the fair application of medication rules. Such approaches and policies are further complicated by the possibility that drug positives may arise from contamination of the equine environment on the backstretch of the race track. This manuscript provides data demonstrating that the general environment of the bac...
King JN, Gerring EL.The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60-min periods at 0.05 mg/kg (n = 4), 0.1 mg/kg (n = 5) and 0.25 mg/kg (n = 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and a...
Von Zup M, Lassaline M, Kass PH, Miller PE, Thomasy SM.Brimonidine is an α2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes. Objective: To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes. Methods: A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonid...
Schutzer WE, Kerby JL, Holtan DW.Trilostane, a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, was administered intravenously to pregnant mares (n = 3) between day 277 and day 282 of gestation to determine its effect on the progestin milieu. In addition, placental tissue from mares at mid-gestation (150-300 days) (n = 4) were exposed to either deuterium-labelled pregnenolone alone or deuterium-labelled pregnenolone and trilostane to examine the effect of trilostane on placental metabolism of pregnenolone. Blood samples were collected from indwelling jugular catheters at frequent intervals for 48 h after infusion...
Ohmura H, Hiraga A, Aida H, Takahashi T, Nukada T.To determine oral dosage and to evaluate the pharmacokinetics in horses of orally administered flecainide, an antiarrhythmic drug, the correlations between its plasma concentration and PR, QRS and QT intervals in equine electrocardiograms (ECG) were investigated. Six healthy horses were administered a randomly ordered dose of 4 or 6 mg/kg of flecainide acetate. The ECG was monitored (heart rate (HR), PR, QRS, and QT intervals) and blood was taken at timed intervals to measure the plasma flecainide concentrations pre- and post-administration. The maximum plasma concentration reached 1014+/-285 ...
Delbeke FT, Debackere M.The prototype of a commercial ELISA test kit designed for fentanyl determination in human urine has been evaluated for screening fentanyl in horse urine and plasma. The measurement of fentanyl after intravenous (2 mg) and intramuscular (0.25 mg) administration in undiluted plasma was not reproducible while accurate quantification of fentanyl in urine greatly depends on the composition of the horse urine. The ELISA assay, however, is simple and could be successfully used for quantitative measurements in diluted urine and for rapid qualitative screening for fentanyl in large numbers of urine sam...
Dumasia MC, Houghton E, Moss MS, Chakraborty J, Marks V.The pro-drugs of dexamethasone, a potent glucocorticoid, are frequently used as anti-inflammatory steroids in equine veterinary practice. In the present study the biotransformation and urinary excretion of tritium labelled dexamethasone were investigated in cross-bred castrated male horses after therapeutic doses. Between 40-50% of the administered radioactivity was excreted in the urine within 24 h; a further 10% being excreted over the next 3 days. The urinary radioactivity was largely excreted in the unconjugated steroid fraction. In the first 24 h urine sample, 26-36% of the total dose was...
