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.
Zientek KD, Anderson DF, Wegner K, Cole C.A method for the extraction and quantitation of procaine in equine plasma was developed for use with liquid chromatography-mass spectrometry (LC-MS). Procaine was isolated from equine plasma by liquid-liquid extraction at pH 11 with dichloromethane using procaine-d10 as an internal standard. Quantitation was achieved by LC-MS using a 3-microm C-18 column coupled to an electrospray ionization source on a linear ion-trap mass spectrometer. The limit of detection and limit of quantitation was determined to be 50 and 200 pg/mL, respectively. The lowest limit of detection determined by previous met...
Kvaternick V, Malinski T, Wortmann J, Fischer J.A sensitive reversed-phase HPLC-UV method was developed for the determination of firocoxib, a novel and highly selective COX-2 inhibitor, in plasma. A 1.0 mL dog or horse plasma sample is mixed with water and passed through a hydrophobic-lipophilic copolymer solid-phase extraction column to isolate firocoxib. Quantitation is based on an external standard curve. The method has a validated limit of quantitation of 25 ng/mL and a limit of detection of 10 ng/mL. The validated upper limit of quantitation was 2500 ng/mL for horses and 10,000 ng/mL for dogs. The average recoveries ranged from 88-93% ...
Struff WG, Sprotte G.Mammals supply their newborn before birth, at birth or shortly after birth with antibodies, immunocytes and humoral constituents. This "borrowed immunity" is a form of passive immunization to protect the newborn against environmental pathogens until it establishes its own pathogen recognition and disposal systems. In cows, goats, horses and some other animal species, most immunoglobulins are obtained from the colostrum, the first milk after birth, via the gut but in humans the majority of immunoglobulins, and those of the IgG-class in particular, are acquired from the mother by placental trans...
Kuchembuck NL, Colahan PT, Zientek KD, Pirman DA, Wegner K, Cole CA.To determine the durations of the local anesthetic effect and plasma procaine concentrations associated with 5- and 10-mg doses of procaine hydrochloride (with or without 100 microg of epinephrine) administered SC over the lateral palmar digital nerves of horses. Methods: 6 healthy adult horses. Methods: The hoof withdrawal reflex latency (HWRL) period was determined by use of a focused heat lamp before and after administration of procaine with and without epinephrine. Blood samples were collected immediately before determination of each HWRL period to assess plasma concentrations of procaine ...
Womble A, Giguère S, Lee EA.The objective of this study was to determine the disposition of orally administered doxycycline in foals. Six healthy 4- to 8-week-old foals were used. Doxycycline was administered to each foal via the intragastric (IG) route at dosages of 10 and 20 mg/kg, in a cross-over design. After the first 10 mg/kg dose, five additional doses were administered at 12-h intervals. A microbiological assay was used to measure doxycycline activity in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Following adminis...
Kvaternick V, Pollmeier M, Fischer J, Hanson PD.The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the eliminatio...
Olsén L, Ingvast-Larsson C, Bondesson U, Broström H, Tjälve H, Larsson P.The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h be...
Delco ML, Nieto JE, Craigmill AL, Stanley SD, Snyder JR.Tegaserod, a serotonin agonist, has been shown to have prokinetic effects in horses, but pharmacokinetic information is not currently available. The pharmacokinetics and in vitro effects of tegaserod were evaluated. Tegaserod increased the contractile activity of smooth muscle preparations of the equine pelvic flexure. Pertinent pharmacokinetic parameters for a single IV and oral dose were determined. Therapeutic plasma concentrations of tegaserod were achieved by a single oral dose at 0.27 mg/kg. These findings indicate that further clinical studies are warranted to investigate potential bene...
Ross DH, Heird C, Byrd JW, Beauchemin V, Kiess W.The safety of a feed-thru pellet formulation containing the insect growth regulator diflubenzuron (0.24%) for control of manure-breeding flies (Musca domestica L. and Stomoxys calcitrans L.) in horses was evaluated. Pellets were administered orally at 0, 1, 3, and 5 times the clinical dosage (0.12 to 0.20 mg/kg) on a daily basis for 31 consecutive days. Variables examined included daily clinical observations, hematology, coagulation, serum chemistry, acetylcholinesterase inhibition, body weights, and physical examinations. Horses remained healthy throughout the study, and no adverse reactions ...
Letendre L, Kvaternick V, Tecle B, Fischer J.A rugged, sensitive and efficient liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative analysis of firocoxib in urine from 5 to 3000 ng/mL and in plasma from 1 to 3000 ng/mL. The method requires 200 microL of either plasma or urine and includes sample preparation in 96-well solid phase extraction (SPE) plates using a BIOMEK 2000 Laboratory Automated Workstation. Chromatographic separation of firocoxib from matrix interferences was achieved using isocratic reversed phase chromatography on a PHENOMENEX LUNA Phenyl-Hexyl column. The mobile phase w...
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...
Nagata S, Kurosawa M, Kuwajima M.A new enzyme immunoassay (EIA) for the measurement of furosemide in horse plasma is described. The lower limit of detection of this EIA method was 7.8 ng/ml. The intra-and inter-assay coefficients of variation ranged from 2.5% to 4.9% and 7.5% to 9.8%, respectively. Cross-reactivity with other compounds was not observed. There was a high correlation (r2=0.987) between the high-performance liquid chromatography and EIA results obtained for furosemide concentrations in horse plasma. These results indicate that the newly developed EIA method is useful for the quantitative analysis of furosemide i...
Vengust M, Staempfli H, Viel L, Heigenhauser G.Horses develop high pulmonary pressures during exercise, which force fluid out of pulmonary capillaries. Specific airway diseases in horses, especially those associated with hypoxaemia, hypercapnoea and acidosis may influence pulmonary haemodynamics and pulmonary interstitial fluid equilibrium. Objective: This study was designed to determine fluid flux (J(V-A) l/min) across the lung in exercising horses treated chronically with acetazolamide. Methods: Six horses were exercised on a treadmill until fatigue without (Con) and with chronic carbonic anhydrase (CA) inhibition (AczTr) and associated ...
Villa R, Cagnardi P, Belloli C, Zonca A, Zizzadoro C, Ferro E, Carli S.The selective COX-2-inhibitor nimesulide is used extra-label in equine veterinary practice as an anti-inflammatory agent. However, there are no data on which to base the rational use of the drug in this species. Objective: To determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. Methods: The pharmacokinetics of nimesulide in the horse after oral administration (1 mg/kg bwt), and oral and i.v. administration (1.5 mg/kg bwt) were investigated, effects of feeding status on bioavailability determined, and plasma protein binding of the drug and ...
Soma LR, Uboh CE, Guan F, McDonnell S, Pack J.Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 ...
Boyer S, Garcia P, Popot MA, Steiner V, Lesieur M.A sensitive and specific method has been developed to detect semi-quantitatively testosterone in horse hair samples. The method involved a washing step with sodium dodecylsulfate aqueous solution. The mane and tail hair samples (100mg) were dissolved in 1 mL of sodium hydroxide for 15 min at 95 degrees C in the presence of d3-boldenone used as internal standard. The next three steps involved diethyl ether extraction and a solid phase extraction on Isolute C18 (EC) cartridges eluted with methanol. The residue was derivatized by adding 100 microL of acetonitrile and 30 microL of PFPA then incuba...
Suarez-Mier G, Giguère S, Lee EA.The objectives of the present study were to determine and compare the pulmonary disposition of azithromycin, clarithromycin, and erythromycin in foals. A single dose (10 mg/kg) of azithromycin, clarithromycin, or erythromycin was administered intragastrically to six healthy 1- to 3-month-old foals using an orthogonal design. Activity of the drugs was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells by use of a microbiologic assay. Peak drug activity in PELF was significantly higher in foals treated with clarithromycin (48.96+/-13.26 microg/mL)...
Carregaro AB, Luna SP, Mataqueiro MI, de Queiroz-Neto A.To investigate spontaneous locomotor activity (SLA) and antinociceptive effects of buprenorphine in horses. Methods: 6 healthy adult horses. Methods: Horses received each of 3 treatments (10 mL of saline [0.9% NaCl] solution, 5 microg of buprenorphine/kg, or 10 microg of buprenorphine/kg). Treatments were administered IV. Order of treatments was randomized, and there was a 10-day interval between subsequent treatments. Spontaneous locomotor activity was investigated in a behavioral box by use of infrared photoelectric sensors connected to a computer, which detected movement of each horse. Anti...
Auer U, Uray C, Mosing M.To investigate the onset and duration of neuromuscular blockade of rocuronium bromide and its associated haemodynamic effects at three doses in healthy horses. Methods: Prospective, randomized experimental study. Methods: Seven adult horses aged 3-20 (mean 10.3) years and weighing 466 +/- 44 (mean +/- SD) kg. Methods: Horses were anaesthetized three times with at least 2 weeks between. They were pre-medicated with 0.6 mg kg(-1) xylazine and 0.01 mg kg(-1) butorphanol i.v.. Anaesthesia was induced with 2.2 mg kg(-1) ketamine and 0.1 mg kg(-1) diazepam i.v.. Following orotracheal intubation anae...
Di Concetto S, Michael Archer R, Sigurdsson SF, Clarke K.A pony undergoing elective castration accidentally received an overdose of IV detomidine (200 microg kg(-1)) before anaesthesia was induced with ketamine and midazolam. A further 100 microg kg(-1) IV dose of detomidine was administered during anaesthesia. The mistake was recognized only when the animal failed to recover from anaesthesia in the expected time. The overdose (300 microg kg(-1) in total) was treated successfully with atipamezole, initially given IV and subsequently IM and titrated to effect to a total dose of 1100 microg kg(-1). The pony regained the standing position. A further in...
Thomasy SM, Mama KR, Whitley K, Steffey EP, Stanley SD.In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. Objective: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. Methods: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthet...
Maes A, Weiland L, Sandersen C, Gasthuys F, De Backer P, Croubels S.A sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2M sodium hydroxide. Ethylmethylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.01 M ammonium acetate and aceto...
Davis JL, Papich MG, Morton AJ, Gayle J, Blikslager AT, Campbell NB.The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-li...
Machnik M, Hegger I, Kietzmann M, Thevis M, Guddat S, Schänzer W.The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentr...
Larenza MP, Landoni MF, Levionnois OL, Knobloch M, Kronen PW, Theurillat R, Schatzmann U, Thormann W.The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods: Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(-1)) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine...
Scheuch E, Spieker J, Venner M, Siegmund W.The long-acting antibiotic tulathromycin is on the marked for treatment of pulmonary infection of cattle, swine and horses. To measure disposition and distribution of tulathromycin in foals, a high throughput method was developed for horse plasma (calibration range: 0.006-0.8 microg/mL) and broncho-alveolar cells (calibration range: 0.1-4.0 microg/10(9)cells) using tandem mass spectrometry. Tulathromycin was extracted from plasma and broncho-alveolar fluid using cation exchange cartridges with acetonitrile/ammonia (95:5, v/v). The chromatography was performed isocratically with a mobile phase ...
Mills PC.The effects of three vehicles, phosphate-buffered saline (PBS), ethanol (50% in PBS w/w) and propylene glycol (50% in PBS w/w) on in vitro transdermal penetration of testosterone was investigated in the horse. Skin was harvested from the thorax of five Thoroughbred horses after euthanasia and stored at -20 degrees C until required. The skin was then defrosted and placed into Franz-type diffusion cells, which were maintained at approximately 32 degrees C by a water bath. Saturated solutions of testosterone, containing trace amounts of radiolabelled [14C]testosterone, in each vehicle were applie...
Murchie TA, Macpherson ML, LeBlanc MM, Luznar S, Vickroy TW.Most current treatments for placentitis in mares are empirical with few control studies to evaluate their effectiveness. Objective: To monitor drug concentrations in allantoic fluid of pregnant pony mares using in vivo microdialysis and establish if this method would be useful for determining allantoic concentrations of drugs in normal mares and those with placentitis. Methods: Five late gestational pony mares had microdialysis probes inserted into the allantoic fluid using transabdominal ultrasound-guided allantocentesis. Single injections of penicillin G (22,000 u/kg), gentamicin (6.6 mg/kg ...
de Macêdo LB, Mouta AN, Araújo-Silva G, Urizar JTP, de Paula VV.Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M ) and 25 mg/kg (M ) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma ...
Easton-Jones CA, Madigan JE, Barnum S, Maxwell LK, Taylor SD, Arnesen T, Pusterla N.Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. Objective: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. Methods: Six horses diagnosed with EMPF. Methods: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 2...
Vissani MA, Zabal O, Tordoya MS, Parreño V, Thiry E, Barrandeguy M.Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those sh...
Brouwer GJ.A total of 103 anaesthetic inductions were performed in horses for a variety of elective procedures. All cases were premedicated with acepromazine maleate (0.02 to 0.05 mg/kg body weight [bwt] intramuscularly [im]). In 50 cases (Group A) anaesthesia was induced by a single intravenous (iv) bolus of thiopentone sodium (11.1 mg/kg bwt or 1 g/90 kg bwt) followed immediately by a bolus of suxamethonium chloride (0.1 mg/kg bwt). In 53 cases (Group B) anaesthesia was induced using iv guaiacol glycerine ether (GGE) (approximately 50 mg/kg bwt) followed by a bolus of thiopentone at half the usual dose...
Ishii H, Obara T, Kijima-Suda I.Paracetamol is used widely as an over-the-counter analgesic and antipyretic medication for humans, but not for Japanese racehorses. Paracetamol can be an environmental substance, and is found together with its two isomers, metacetamol and orthocetamol, in equine urine. However, the sources and routes of paracetamol exposure remain unclear. To control the misuse of paracetamol, it is appropriate to establish residue limits for paracetamol to differentiate the administration of paracetamol from its environmental levels. In this study, we developed and validated a quantitative method for paraceta...
Higgins AJ, Lees P, Sedgwick AD, Buick AR, Churchus R.In a two-part cross-over experiment in six ponies, an acute inflammatory reaction was generated by injecting carrageenin solution into subcutaneously-implanted tissue-cages lined with fibrovascular granulation tissue. In each part of the cross-over, half of the ponies received a novel phenylpyrazoline anti-inflammatory agent (BW540C) orally and half received a placebo treatment. BW540C inhibited platelet cyclo-oxygenase for 24 h but the reductions in exudate eicosanoid concentrations were less pronounced. A significant suppression in the rise of surface skin temperature in BW540C-treated ponie...
Stover SM, Brown MP, Kelly RH, Farver TB, Knight HD.Six adult mares were given a single dose of aqueous suspension procaine penicillin G (300,000 IU/ml) IM at a dosage of 22,000 IU/kg of body weight (15.4 mg of penicillin G/kg). Serum, synovial fluid, peritoneal fluid, and urine penicillin concentrations were measured serially over a 48-hour period. The mean peak serum penicillin concentration was 1.42 microgram/ml at 3 hours. Penicillin was detected in synovial fluid and peritoneal fluid, which obtained mean peak penicillin concentrations of 0.62 microgram/ml and 0.58 microgram/ml, at 4 hours and 3 hours, respectively. These concentrations ste...
Weiss DJ, Evanson OA, McClenahan D, Fagliari JJ, Dunnwiddie CT, Wells RE.To determining whether inhibition of platelet aggregation prevents development of carbohydrate overload-induced alimentary laminitis. Methods: 22 healthy adult ponies. Methods: Acute laminitis was induced by oral administration of corn starch/wood flour to 16 ponies, 8 of which were treated with a synthetic analogue of the platelet fibrinogen receptor antagonist peptide (RPR) RGDS (arginine-glycine-aspartic acid-serine) 110885; 6 ponies served as negative controls. Blood was collected before and at 4, 8, 12, 24, 28, and 32 hours after administration of carbohydrate overload, and PCV, total pla...
Vaala WE.Other therapeutic agents used in foals for specific diseases are discussed elsewhere. The marked effect of species, age, and degree of maturity on drug metabolism in the neonate reinforces the danger of interspecies extrapolation of pharmacology, the need for information specific for the foal, and the necessity for monitoring drug levels in the individual. Suggested antimicrobial doses are listed in Tables 3, 4, and 6. Recommended doses of anticonvulsants and sedatives are listed in Table 8 and in the article "Intensive Care of the Neonatal Foal." The following are recommendations for drug the...
Farnsworth KD, White NA, Robertson J.To determine the effect of intra-articular gentamicin-impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma. Methods: Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin-impregnated PMMA on normal equine tarsocrural joints. Methods: Five healthy adult horses. Methods: Gentamicin-impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) we...
Dirikolu L, Karpiesiuk W, Lehner AF, Hughes C, Granstrom DE, Tobin T.Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of abs...
Wichtel MG, Breuhaus BA, Aucoin D.Pharmacokinetic values after IV administration of amikacin sulfate were determined for clinically normal and hospitalized foals during the first week of life. The relations between drug disposition and sepsis score and serum creatinine concentration also were studied. In clinically normal foals, differences in sepsis score, serum creatinine concentration, and pharmacokinetic variables of amikacin were not found between foals 1 to 3 and 4 to 7 days old. In hospitalized foals, sepsis score, serum creatinine concentration, area under the curve, area under the moment curve, and mean residence time...
Javsicas LH, Sanchez LC.Administration of omeprazole paste per os to healthy neonatal foals has been shown to effectively increase intragastric pH, but has not been evaluated in sick neonatal foals. Objective: To determine the effect of orally administered omeprazole paste on intragastric pH in clinically ill neonatal foals requiring nasogastric intubation. Methods: Intragastric pH was measured continuously for 24 h using an indwelling electrode and continuous data recording system in hospitalised neonatal foals age < or =2 days. Intragastric pH was measured for 12 h prior to (pretreatment period) and 12 h followi...
Love DN, Rose RJ, Martin IC, Bailey M.Amoxycillin trihydrate was administered orally to 6 foals at dose rates of 13 mg/kg (low), 20 mg/kg (medium) and 30 mg/kg (high) and serum concentrations determined at intervals up to 8 h. Therapeutic serum levels of 1 microgram/ml persisted for 268 mins at a dose rate of 13 mg/kg, for 339 mins at 20 mg/kg and for 381 mins at 30 mg/kg. A 2 micrograms/ml serum level persisted for 198 mins at a dose rate of 13 mg/kg, for 268 mins at 20 mg/kg and for 311 mins at 30 mg/kg. To determine the spectra of its antibacterial activity, the minimum inhibitory concentrations of amoxycillin against 8 genera ...
Gasthuys F, Parmentier D, Goossens L, De Moor A.Romifidine (STH 2130-Cl or Sedivet) is an alpha 2-agonistic imino-imidazol sedative for intravenous use in horses recently developed by Boehringer Ingelheim, Vetmedica GmbH. An exploratory study was done in nine warm-blood horses, randomly divided into three groups, which received different dosages of romifidine (0.04, 0.08 and 0.12 mg/kg of body weight (BWT) intravenously (i.v.)) with at least one week's interval between tests. Romifidine induced a marked bradycardia accompanied by second degree atrioventricular (AV) block and some sinus blocks at all tested dosages. A placebo (NaCl 0.9% i.v....
Gerring EL, King JN.Cisapride and domperidone were both effective in restoring electrical and mechanical activity, coordination between gastric and small intestinal activity cycles and the stomach to anus transit time in three ponies in which post operative ileus was induced experimentally. Cisapride (0.1 mg/kg bodyweight intramuscularly) for three to eight doses prevented idiopathic post operative ileus in 22 clinical cases requiring colic surgery. The only side effects after cisapride were increased bowel sounds and slight, transient sounds of discomfort. No adverse side effects were seen in 16 cases following ...
Tennent-Brown BS, Epstein KL, Whelchel DD, Giguère S.To evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses. Methods: Randomized crossover study. Methods: Large animal veterinary teaching hospital. Methods: Six adult mixed breed healthy mares. Methods: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R-time (R), K-time (K), angle (ANG), and maxim...
Re G, Badino P, Odore R, Galaverna D, Girardi C.To determine the concentration and binding characteristics of alpha-adrenoceptor subtypes in smooth muscle cell membranes of equine ileum. Methods: Segments of longitudinal and circular smooth muscle from the ileum of 8 male and 8 female adult horses. Methods: Distribution of alpha-adrenoceptor subtypes was assessed by use of radioligand binding assays incorporating [3H]-prazosin and [3H]-rauwolscine, highly selective alpha1- and alpha2-adrenoceptor antagonists, respectively. Characterization of adrenoceptor subtypes was performed by use of binding inhibition assays. Results: On the basis of b...
Wilson WD, Spensley MS, Baggot JD, Hietala SK.The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body....
Hopster K, Soma LR, Li X, Hopster-Iversen C, Boston RC, Driessen B.Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg hr for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration-time curves following bolus an...
Gerring EL.The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation,...
Fontenot RL, Langston VC, Zimmerman JA, Wills RW, Sloan PB, Mochal-King CA.To determine meropenem concentrations in radiocarpal (RC) joint fluid and plasma after intravenous regional limb perfusion (IVRLP). Methods: In vivo experimental study. Methods: Nine healthy adult mares. Methods: Meropenem (500 mg) was injected in the forelimb of standing sedated horses via IVRLP with a pneumatic tourniquet inflated to 400 mmHg. Synovial fluid was collected from RC joints at 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours after meropenem injection. Blood samples were collected from the jugular vein at the same time points and at 5 and 15 minutes following injection. Meropenem concentr...
Fletcher DJ, Brainard BM, Epstein K, Radcliffe R, Divers T.Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. Objective: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in...
Kilcoyne I, Dechant JE, Nieto JE.The objective of the article is to determine the synovial fluid concentrations of amikacin sulfate (AS) after performing an intravenous regional limb perfusion (IVRLP) with the tourniquet in place for 10 minutes and compare this with 30 minutes. This is a randomised crossover experimental design. Animals were seven healthy adult horses. Horses underwent two IVRLP procedures in a randomised, crossover design. The horses received IVRLP with 2 g AS diluted to 60 ml using 0.9% saline in the cephalic vein of alternate limbs with the tourniquet in place for either 10 or 30 minutes, with a ...
Gray AW, Davies ME, Jeffcott LB.Equine osteoclast-like cells (OCLs) were generated from the bone marrow (BM) of two ponies and one horse in the presence of RANKL, the receptor activator of NF kappa B ligand and macrophage colony-stimulating factor (M-CSF). The phenotype of these cells was confirmed by demonstration of characteristics typical of osteoclasts (OCs) including: the expression of tartrate-resistant acid phosphatase (TRAP), the vitronectin receptor (VNR) and the calcitonin receptor (CTR), the demonstration of responsiveness to calcitonin (CT) and the ability to form resorption lacunae on ivory slices and calcium ph...
Adam-Castrillo D, White NA, Donaldson LL, Furr MO.To determine effects on anal pressure of horses after local injection of the external anal sphincter with Clostridium botulinum toxin type B. Methods: 11 healthy adult horses. Methods: Peak and resting anal sphincter pressures were measured with a custom-made rectal probe that was connected to a pressure transducer. Pressures were measured before treatment and after injection with botulinum toxin type B (BTB) or saline (0.9% NaCl) solution. Dose titration with 500, 1,000, 1,500, and 2,500 U of BTB was completed. Physical changes, behavior, and anal pressure were recorded for each horse. Result...
Chen CL, Zhu D, Gillis KD, Meleka-Boules M.To develop a simple and sensitive ELISA for detection of dexamethasone in horse serum and urine. Methods: Blood and urine samples from 3 thoroughbred mares. Methods: A dexamethasone oxime was prepared and conjugated to hemocyanin, bovine serum albumin and to horseradish peroxidase. One- and two-step double-antibody ELISA methods, as well as a radioimmunoassay method, were performed. The one-step ELISA was used to test urine from 3 Thoroughbred mares injected with 5 mg of dexamethasone, IV. Results: The ELISA could detect dexamethasone in the range of 0.01 to 50 ng/ml, with intra- and interassa...
Sundra T, Kelty E, Rendle D.An extended-release injectable omeprazole formulation (ERIO) has become a popular treatment for equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) where it is available; however, published data are limited and optimal treatment regimens have not been determined. Objective: To compare effects of treatment on ESGD and EGGD when an ERIO formulation is administered at either 5- or 7-day intervals. Methods: Retrospective clinical study. Methods: Case records and gastroscopy images of horses with ESGD or EGGD treated with ERIO were reviewed. Images were anonymised and...
Bailey DN.The relative binding of acetaminophen, lidocaine, phenobarbital, procainamide, quinidine, and theophylline to sera of seven mammalian species was studied. Pooled commercial sera from cow, goat, horse, human, pig, rabbit, and sheep were supplemented with 5 and 10 mM concentrations of each drug. For each serum, each drug, and each drug concentration, equilibrium dialysis was performed in duplicate against phosphate buffer (pH 7.4, 0.1 M, 4 degrees C). Percent drug bound to serum was calculated. Phenobarbital demonstrated more than 20% binding to goat, horse, human, and sheep serum at both 5 and ...
Burton AJ, Giguère S, Warner L, Alhamhoom Y, Arnold RD.Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrat...
