Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Brown MP, Kelly RH, Stover SM, Gronwall R.Six healthy adult mares were given a single IV injection of trimethoprim (TMP)-sulfadiazine (SDZ) at a dosage rate of 2.5 mg of TMP/kg of body weight and 12.5 mg of SDZ/kg. Serum, synovial, peritoneal, and urine TMP-SDZ concentrations were measured serially over a 48-hour period. The highest measured mean concentrations of TMP and SDZ were found in the first (0.5 hour) sample of serum, synovial fluid, and peritoneal fluid. The mean peak concentrations of TMP and SDZ averaged 4.37 micrograms/ml and 21.81 micrograms/ml for serum, 2.95 micrograms/ml and 15.31 micrograms/ml for synovial fluid, and...
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...
Brimijoin S, Mintz KP, Prendergast FG.Interactions between dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA) and the cholinesterases were examined by the techniques of enzyme kinetics and fluorescence spectroscopy. When tested with partially purified enzyme preparations, DAPA was a potent inhibitor of butyrylcholinesterase (IC50 = 2 x 10(-7) M) but not of acetylcholinesterase (IC50 = 4 x 10(-4) M). For a detailed study of the effects of DAPA on butyrylcholinesterase (BuChE), the enzyme was purified to homogeneity from horse serum, with the aid of affinity chromatography on N-methyl acridinium. The kinetics of the inhibition o...
Katano Y, Imai S.The effects of dipyridamole on thromboxane A2 formation by horse platelet microsomes were studied in comparison with those of imidazole, a prototype inhibitor of TXA2 synthetase and nifedipine, a calcium antagonistic vasodilator. Thromboxane A2 was synthesized by incubating PGH2 with horse platelet microsomes and was assayed on the superfused rabbit aorta. Dipyridamole induced as strong an inhibition of TXA2 synthesis as imidazole, while nifedipine was without effects. The possible beneficial clinical outcomes of this effect of dipyridamole are discussed.
Brightman AH, Manning JP, Benson GJ, Musselman EE.Schirmer I tear tests were conducted on 14 horses. The test was performed before and after IV administration of xylazine hydrochloride, during maintenance anesthesia with halothane in oxygen, and 3 hours after discontinuation of anesthesia. Xylazine hydrochloride did not decrease tear production from the mean base-line value of 23.94 +/- 5.23 mm/min after its IV administration. Tear production was decreased to mean values of 15.57 +/- 4.29 mm/min at 30 minutes and 13.84 +/- 4.25 mm/min at 60 minutes during the maintenance of halothane anesthesia. Three hours after anesthesia was discontinued, ...
Lyons ET, Tolliver SC, Drudge JH.Seven critical tests in equids were conducted with single doses of fenbendazole (5 mg kg-1) alone (Panacur--American Hoechst, Somerville, NJ); (2 tests with paste and 1 with suspension formulation) or in combination with piperazine (American Hoechst); (40 mg base kg-1); (4 tests with paste formulation). The main purpose of the tests was evaluation of activity against benzimidazole-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus). Natural infections of 2 populations of benzimidazole-resis...
Love DN, Rose RJ, Martin IC, Bailey M.Twelve geldings were used to evaluate serum levels of penicillin following the intravenous (iv) and intramuscular (im) injection of benzylpenicillin, im procaine penicillin and im fortified benzathine penicillin, at a variety of dose rates. Blood samples were collected up to 7 h after iv and im benzylpenicillin, up to benzathine penicillin. Results were analysed using an analysis of variance and regression analyses were used to calculate the time taken for the serum penicillin concentration to decline to 0.5 micrograms/ml. As a result of the experiments the following dosage regimes could be re...
Morris DD, Fregin GF.Seventy-seven horses with atrial fibrillation (AF) were treated orally with quinidine sulfate (QS) at the University of Pennsylvania, School of Veterinary Medicine, Thirty-seven horses (48%) had adverse reactions to QS, the most common of which were nasal mucosal edema, anorexia, colic, and diarrhea. The mean highest daily QS dose was slightly greater in horses showing toxicity (P less than 0.1) and their conversion rate was less (P less than 0.05). A schedule of gradually increasing QS dose was time consuming, costly and not associated with fewer adverse reactions. Horses were compared by the...
Muir WW, Sams RA, Huffman RH, Noonan JS.The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted ...
Brown MP, Stover SM, Kelly RH, Farver TB.Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 micrograms/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 micrograms/ml and 3.92 micrograms/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and w...
Campbell WC.The avermectins are macrocyclic lactones produced by Streptomyces avermitilis. One of them has been chemically modified and given the non-proprietary name ivermectin. The compounds have shown efficacy against various stages of filarial parasites. With respect to pre-adult stages in the mammalian host, activity has been observed against Dirofilaria immitis in ferrets and dogs, and Dipetalonema viteae and Litomosoides carinii in jirds (Meriones); but activity has not been observed against the developing stages of Brugia spp. in jirds or Onchocerca spp. in cattle. The compounds have not shown act...
Skrabalak DS, Maylin GA.Dexamethasone and a metabolite, 9-fluoro-16α-methyl-6β, 11β, 16β-trihydroxy-1, 4-androstadiene-3, 17-dione, were detected in the urine of horses injected parenterally with the parent drug. The structure of the metabolite was elucidated by thin-layer chromatography, infrared spectroscopy, mass spectroscopy and nuclear magnetic resonance spectroscopy.
Brown MP, Stover SM, Kelly RH, Farver TB.Six adult mares were given a single dose of ampicillin trihydrate (250 mg/ml) intramuscularly at a dosage of 20 mg/kg body weight. Serum, synovial fluid, peritoneal fluid and urine ampicillin concentrations were measured serially over a 48 h period. The mean peak serum ampicillin concentration was 2.49 micrograms/ml at 6 h. Ampicillin was found in synovial fluid and peritoneal fluid, which obtained mean peak ampicillin concentrations of 1.65 micrograms/ml and 1.81 micrograms/ml at 6 h and 4 h respectively. These concentrations declined in parallel with serum concentrations and were still detec...
Brown MP, Stover SM, Kelly RH, Farver TB.Six healthy adult mares were given a single dose of kanamycin sulfate (200 mg/ml) IM at a dosage rate of 5 mg/kg of body weight. Kanamycin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum kanamycin concentration was 12.55 microgram/ml at 1 hour. Mean peak kanamycin concentrations in synovial fluid and peritoneal fluid were 7.25 microgram/ml and 9.27 microgram/ml at 2 hours and 3 hours, respectively. These concentrations decreased steadily in parallel with serum concentrations and were still measurable at 48 h...
Stover SM, Brown MP, Kelly RH, Farver TB.Six healthy adult mares were given a single dose (25 mg/kg of body weight) of sodium oxacillin IM. Oxacillin concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The mean peak serum oxacillin concentration was 9.75 microgram/ml at 0.5 hour after injection. Mean peak oxacillin concentrations in synovial and peritoneal fluids were 1.45 microgram/ml and 2.60 microgram/ml at 1 hour and 2 hours, respectively. These concentrations decreased in parallel with serum values and were not measurable at 48 hours. Urine concentrations of oxacilli...
McGuirk SM, Muir WW, Sams RA.A pharmacokinetic study was made, using 7 healthy adult horses (weighing between 400 and 560 kg) given quinidine gluconate IV and quinidine sulfate orally. The apparent volume of distribution of quinidine base was 3.10 +/- 0.79 L/kg, total body clearance was 5.49 +/- 2.40 ml/minute/kg, and plasma half-life was 6.65 +/- 3.00 hours. The systemic availability of quinidine sulfate after oral administration of a 10 mg/kg dose was 48.5 +/- 20.4%. Oral administrations of quinidine sulfate in doses of 10 mg/kg and 10 g produced peak plasma concentrations of 0.79 microgram/ml at 146 minutes and 1.47 mi...
Garcia-Villar R, Toutain PL, Alvinerie M, Ruckebusch Y.The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half-life (t1/2 beta) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half-life (t1/2 alpha) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the pla...
Combie J, Shults T, Nugent EC, Dougherty J, Tobin T.The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more tha...
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...
Brown MP, Stover SM, Kelly RH, Farver TB, Knight HD.Six adult mares were given a single intravenous injection of oxytetracycline HCl (50 mg/ml) at a dosage of 5 mg/kg. Serum, synovial fluid, peritoneal fluid, and urine oxytetracycline concentrations were measured serially over a 48-h period. The highest measured serum oxytetracycline concentration was 8.01 mcg/ml at 1/2 h. Oxytetracycline was detected in synovial fluid and peritoneal fluid, which obtained mean peak oxytetracycline concentrations of 4.43 mcg/ml and 4.20 mcg/ml, at 1/2 h and 1 h, respectively. These concentrations steadily declined in parallel with serum concentrations and were n...
Shapland JE, Garner HE, Hatfield DG.Clenbuterol, a bronchospasmolytic agent (beta 2 agonist) was studied in terms of its hemodynamic and airflow response in eight, healthy horses. Four animals were instrumented to record intrapleural pressure and air flow, these were used to compute pulmonary resistance, peak flow rates, and tidal volumes. Four animals were instrumented to record pulmonary arterial pressure, carotid arterial pressure, cardiac output, and arterial gas tensions. After control values were recorded, clenbuterol (0.8 microgram/kg) was intravenously administered to each horse in each experiment group. Following clenbu...
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 ...
Hubbell JA, Muir WW, Sams RA.We determined the cardiopulmonary changes in horses given guaifenesin alone and in the same horses given xylazine (IV) immediately before administration of guaifenesin. In addition, plasma guaifenesin concentrations were determined in horses and 2 pregnant mares and compared with previously published values in ponies. The dose of guaifenesin necessary to produce lateral recumbency in adult horses was 134 +/- 34 mg/kg (mean +/- SD). The administration of guaifenesin caused insignificant (P less than 0.05) changes in heart rate, respiratory rate, right atrial pressure, pulmonary arterial pressur...
Gill KK, Kroeger EA.Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally a...
Cenani A, Brosnan RJ, Madigan S, Knych HK, Madigan JE.Propranolol has been suggested for anxiolysis in horses, but its sedation efficacy and side effects, both when administered alone and in combination with α-adrenoceptor agonists, remain undetermined. This study aimed to document the pharmacokinetics and pharmacodynamics of propranolol, romifidine and their combination. Methods: Randomized, crossover study. Methods: Six adult horses weighing 561 ± 48 kg. Methods: Propranolol (1 mg kg; treatment P), romifidine (0.1 mg kg; treatment R) or their combination (treatment PR) were administered intravenously with a minimum of 1 week between treatment...
Castro LA, Brown MP, Gronwall R, Houston AE, Miles N.Six foals from 6 to 8 weeks of age were given a single oral dose of rifampin at a dosage of 10 mg/kg of body weight. Serum rifampin concentrations were measured serially during a 24-hour period. The mean peak serum rifampin concentration was 6.7 micrograms/ml at 4 hours after treatment. The concentration decreased slowly, and at 24 hours the mean value was 2.7 micrograms/ml. The elimination half-life was 17.5 hours, and the elimination rate constant was 0.04/hr.
Takeda A, Tanaka H, Shinohara T, Ohtake I.A sample preparation method for mass chromatographic detection of doping drugs from horse plasma is described. Bond Elut Certify (1 g/6 ml) is used for the extraction of 4 ml of horse plasma. Fractionation is performed with 6 ml of CHCl3-Me2CO (8:2) and 5 ml of 1% TEA-MeOH according to its property. Simple and effective clean-up based on non-aqueous partitioning is adopted to remove co-eluted contaminants in both acid and basic fractions. Two kinds of 1-(N,N-diisopropylamino)-n-alkanes are co-injected with the sample into the GC-MS system for the calculation of the retention index. Total recov...
Soraci AL, Mestorino ON, Errecalde JO.The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0....
Bennett RC, Steffey EP, Kollias-Baker C, Sams R.To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles. Methods: 6 healthy adult horses. Methods: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, i.v.) administration followed immediately by i.v. administration of saline (0.9% NaCI) solution, lo...
Kutter AP, Bettschart-Wolfensberger R, Schwarzwald CC, Portier KG, Ringer SK.To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses. Methods: Prospective, experimental trial. Methods: Nine adult horses weighing a median (range) of 535 (470-602) kg. Methods: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar pl...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
Freeman DE, Inoue OJ, Eurell TE.To study the effect of flunixin meglumine on short circuit current (Isc) in equine right ventral colon in vitro. Methods: Intestinal mucosa from healthy horses and ponies. Methods: Isc was measured in mucosa from the right ventral colon mounted in Ussing chambers. In experiment 1, collection and incubation solutions were: control (no additions); flunixin meglumine, 4 micrograms/ml; indomethacin, 10(-6) M; and flunixin meglumine (4 micrograms/ml) with 10(-6) M prostaglandin E2. In experiment 2, incubation conditions were: control [plain Krebs-Ringer bicarbonate [KRB] solution]; flunixin meglumi...
Nichols CL, Doherty TJ, Schumacher J, Jones PD, Sun X.To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone. Methods: 8 mares with no signs of lameness. Methods: In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexme...
Brotherton HO, Yost RA.A screening and confirmation procedure for drugs and metabolites in the blood serum and urine of racing animals was developed. Equine blood serum was spiked with low concentrations of several drugs of interest. Canine blood serum and urine were collected following oral doses of diethylcarbamazine, procaine, and phenylbutazone. Serum, urine, and extracts of each were analyzed, using a triple quadrupole mass spectrometer. Simultaneous screening of up to 50 drugs was possible in a single sample, in less than 2 minutes. Detection limits for most compounds were in the ng/ml to microgram/ml range, u...
Tobin T, Blake JW, Tai CY, Arnett S.Rapid intravenous injection of 1 g of procaine hydrochloride in Thoroughbred mares produced variable signs of central nervous system excitation for as long as 4 minutes. Plasma concentrations of procaine were similarly variable and transient, decreasing with a half-life of approximately 25 minutes. In vitro, plasma from freshly collected equine blood hydrolyzed procaine with a half-life of approximately 7.5 minutes. This hydrolysis was apparently due to plasma esterases. Penicillin, when added free or complexed as procaine-penicillin, did not protect procaine against hydrolysis by these plasma...
Zertuche JM, Brown MP, Gronwall R, Merritt K.Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with ...
Camargo FC, Robinson NE, Dirikolu L, Berney C, Eberhart S, Derksen FJ, Lehner AF, May J, Hughes C, Tobin T.Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, DeTolve P, Derksen FJ, Harkins JD, Lehner AF, Tobin T.Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. Objective: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural...
Beech J, Kohn C, Leitch M, Weinstein AJ, Gallagher M.Serum, synovial fluid, and urine concentrations of gentamicin were measured in normal mature horses which had been given a single dose of the drug. Mean peak serum concentration (16.8 microgram/ml) occurred in horses 30 minutes after they were given a single intramuscular dose of 4.4 mg of gentamicin/kg of body weight. In horses given a smaller dose of gentamicin (1.7 mg/kg), mean peak serum concentrations of gentamicin (10.2 microgram/ml) appeared at 1 hour. Synovial fluid concentration was maximum at 2 hours for both doses; in horses given the larger dose, mean peak concentration was 6.4 mic...
Barton AK, Gehlen H.The term remodeling describes the process resulting in a tissue that is structurally and architecturally altered compared to its healthy counterpart. At least in severe equine asthma, this occurs mainly, but not exclusively, as a consequence of neutrophilic airway inflammation and is characterized by hypertrophy of the smooth muscle layers in airway and arterial walls as well as fibrosis of the bronchial walls and pulmonary interstitial tissue. To date, much less is known for mild to moderate equine asthma. For a long time it was assumed that these processes are irreversible, and at least for ...
Schellenberg LM, Regenthal R, Abraham G.The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
Baggot JD, Love DN, Rose RJ, Raus R.The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (+/- sd) peak serum concentration of 23.2 +/- 10.2 micrograms/ml present at 30 mins, and at 8 h the serum concentration was 2.8 +/- 0.8...
Marr K, Marsh K, Hernandez L, Cunningham FM, Lees P.Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, possess properties consistent with their involvement in a range of inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily) was absorbed from the gastrointestinal tract, and penetrated readily into tissue cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6). Ionophore-stimulated leukotriene (LT) B4 synthes...
Rauws AG, van Schothorst M, Frik JF.The protein binding, the plasma half-life and the residue depletion of sulfamonomethoxine (SMM) after intramuscular administration were investigated in pigs, horses and cattle. Protein binding was weakly concentration-dependent. The bound fraction in plasma in the therapeutic range amounted to approximately 45, 40 and 50% for pigs, horses and cattle respectively, and the plasma half-lives were approximately 5.1, 5.7 and 3.1 hours respectively. SMM levels were less than 1 mug/g in muscle tissue after 36, 20 and 12 hours in pigs, horses and cattle respectively. In the kidney SMM levels were not ...
Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK.Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Duvivier DH, Votion D, Vandenput S, Art T, Lekeux P.Development of dry powder inhalation (DPI) for horses requires the use of an adapted face mask. In experiment I, 4 masks (A, B, C and D) were tested and factors influencing the delivery of the dry powder were determined. Mask A was one which is commercially available for metered-dose inhalation. Mask B had the same shape as Mask A but an airtight rubber seal was added for the connection between the mask and horse's head. Mask C was a prototype adapted for DPI with connection for the DPI device between the nostrils, airtight expiratory valves in front of each nostril and airtight rubber seal to...
LeBlanc M, Neuwirth L, Mauragis D, Klapstein E, Tran T.The effects of oxytocin on the percentage of technetium 99m albumin colloid (99mTc-microAA), cleared from the uterine lumen was measured in 13 mares. Scintigraphy was performed during 4 consecutive oestrous cycles, on Day 3 of oestrus during Cycles one and 3 and 48 h after ovulation during Cycles 2 and 4. Oxytocin (20 iu) was given i.v. after the initial scintigraphy image during Cycles 3 and 4. Seven multiparous mares (Group 1) were classified as 'susceptible' and 6 mares (2 nulliparous and 4 multiparous; Group 2) were classified as 'resistant' to endometritis. All mares cleared > 90% of 99mT...
Sarasola P, McKellar QA.The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
Velasco-Murillo V.It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug admi...
Gupta T, Chatterjee A.Pregnant mare's serum gonadotropin (PMSG) of 10 IU on day 5 of pregnancy induced luteal demise and consequently an absolute resorption of fetuses and placentae resulted on day 16 of pregnancy. Simultaneous regimen of PMSG and indomethacin or cortisone was found to be consistently effective in preventing the luteolytic effect of PMSG. The growth of the fetuses, placentae as well as corpora lutea was found to be parallel to controls. Similarly, shortening of the duration of pseudopregnancy to 10--12 days in the bilaterally hysterectomized rat by PMSG and its retaining the normal duration of 18--...
Cohen ND, Chu KK, Stanley SD, Wang N.To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. Methods: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis ...
Knych HK, Stanley SD, McKemie DS, Arthur RM, Bondesson U, Hedeland M, Thevis M, Kass PH.Although developed as a therapeutic medication, meldonium has found widespread use in human sports and was recently added to the World Anti-Doping Agency's list of prohibited substances. Its reported abuse potential in human sports has led to concern by regulatory authorities about the possible misuse of meldonium in equine athletics. The potential abuse in equine athletes along with the limited data available regarding the pharmacokinetics and pharmacodynamics of meldonium in horses necessitates further study. Eight exercised adult thoroughbred horses received a single oral dose of 3.5, 7.1, ...
Brown MP, Kelly RH, Gronwall RR, Stover SM.Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloram...
