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.
Harkins JD, Woods WE, Lehner AF, Fisher M, Tobin T.Clenbuterol is a beta2 agonist/antagonist bronchodilator marketed as Ventipulmin and is the only member of this group of drugs approved by the US Food and Drug Administration (FDA) for use in horses. Clenbuterol is a class 3 drug in the Association of Racing Commissioners International (ARCI) classification system; therefore, its identification in postrace samples may lead to sanctions. Recently, the sensitivity of postrace testing for clenbuterol has been substantially increased. The objective of this study was to determine the 'detection times' for clenbuterol after administration of an oral...
Errecalde JO, Carmely D, Mariño EL, Mestorino N.The serum and synovial pharmacokinetics of amoxycillin (AMX) were studied after i.v. administration at a dosage of 40 mg/kg to normal horses and horses with induced aseptic carpal arthritis. The best estimates of serum and synovial pharmacokinetic parameters were calculated by mono or bivariable non-linear regression analysis. A biexponential equation was used to describe the concentration vs. time profiles in both normal and arthritic horses. There were no serum kinetic differences between normal and arthritic horses. There were, however, major synovial kinetic changes between these groups. T...
Matthews NS, Peck KE, Taylor TS, Mealey KL.To describe the pharmacokinetics of phenylbutazone and oxyphenbutazone after IV administration in miniature donkeys. Methods: 6 clinically normal miniature donkeys. Methods: Blood samples were collected before and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration of phenylbutazone (4.4 mg/kg of body weight). Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each donkey was analyzed separately to estimate model-i...
Willis AM, Robbin TE, Hoshaw-Woodard S, Wilkie DA, Schmall ML.To evaluate the effect of topical administration of 2% dorzolamide hydrochloride or 2% dorzolamide hydrochloride-0.5% timolol maleate on intraocular pressure (IOP) in clinically normal horses. Methods: 18 healthy adult horses without ocular abnormalities. Methods: The IOP was measured at 5 time points (7 AM, 9 AM, 11 AM, 3 PM, 7 PM) over 11 days. On days 1 and 2, baseline values were established. On days 3 through 5, horses received 2% dorzolamide HCI (group D, n = 9) or 2% dorzolamide HCl-0.5% timolol maleate (group DT, 9) in 1 randomly assigned eye every 24 hours immediately following each d...
Peck KE, Hines MT, Mealey KL, Mealey RH.To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses. Methods: 5 horses with adult-onset narcolepsy. Methods: Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed se...
Soma LR, Uboh CE, Guan F, Birks EK, Teleis DC, Rudy JA, Tsang DS, Watson AO.To determine pharmacokinetics and excretion of phenytoin in horses. Methods: 6 adult horses. Methods: Using a crossover design, phenytoin was administered (8.8 mg/kg of body weight, IV and PO) to 6 horses to determine bioavailability (F). Phenytoin also was administered orally twice daily for 5 days to those same 6 horses to determine steady-state concentrations and excretion patterns. Blood and urine samples were collected for analysis. Results: Mean (+/- SD) elimination half-life following a single IV or PO administration was 12.6+/-2.8 and 13.9+/-6.3 hours, respectively, and was 11.2+/-4.0 ...
McKinney AR, Ridley DD, Suann CJ.After oral administration to a thoroughbred gelding, the anabolic steroid norethandrolone was converted into a complex mixture of oxygenated metabolites. These metabolites were extracted from the urine, deconjugated by methanolysis and converted to their O-methyloxime trimethylsilyl derivatives. Gas chromatographic/mass spectrometric analysis indicated the major metabolites to be 19-norpregnane-3,16,17-triols, 19-norpregnane-3,17,20-triols and 3,17-dihydroxy-19-norpregnan-21-oic acids. Some minor metabolites were also detected.
Boeckh S, Buchanan C, Boeckh A, Wilkie S, Davis C, Buchanan T, Boothe D.Following approval of a concentrated injectable formulation of enrofloxacin for cattle (Baytril 100 Injectable, Bayer Corp. Agricultural Division, Shawnee Mission, KS), equine practitioners have started administering this preparation both parenterally and orally to horses, despite the lack of pharmacokinetic data in this species. Six healthy horses received enrofloxacin at 7.5 mg/kg both orally and intravenously, with the sequence being randomly assigned and at least 1 week of washout allowed between administrations. Blood samples were collected from each horse at various intervals after drug ...
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 ...
Wyse CA, Murphy DM, Preston T, Morrison DJ, Love S.The aim of this study was to assess the feasibility of applying the 13C-octanoic acid breath test for assessment of gastric emptying in ponies by investigating the pattern of 13C enrichment in breath following the administration of a test meal +/- 13C-octanoic acid. After a 14 h fast, the ponies received either no meal (Test I) or a standardised test meal labelled with 0 mg (Test II), 125 mg (Test III), 250 mg (Test IV) or 500 mg (Test V) 13C-octanoic acid. For each test (I-V), exhaled breath samples were collected in duplicate at 1 h and immediately before ingestion of the test meal and at fr...
Chu KK, Wang N, Stanley S, Cohen ND.The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulti...
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...
Orsini JA, Spencer PA.A dose-response study was undertaken of the effects of a newly developed histamine type 2 receptor antagonist, BMY-26539-01, on gastric acid secretion in 4 fasted horses. Doses of 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, or placebo were administered in a randomly assigned treatment sequence. Hydrogen ion concentration and pH were variable during baseline measurements in all 4 animals; however, following BMY-26539-01 administration, mean pH increased and hydrogen ion concentration decreased in a dose-related pattern. At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and >...
Simpson BS.Psychotropic drugs are used by veterinary behavior specialists and general veterinary practitioners to treat behavior problems of companion animals. Dogs, cats, pet birds, horses, and zoo animals benefit from this type of therapy. However, many drugs used to treat anxiety or depression in animals were designed for use in human patients. Compounding is a critical step in adapting those medications for use in different species. Formulations that improve palatability or facilitate administration can often determine the success or failure of therapy in veterinary patients, and compounding is often...
Sellon DC, Monroe VL, Roberts MC, Papich MG.To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. Methods: 10 healthy adult horses. Methods: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, a...
Campbell NB, Blikslager AT.Cyclooxygenase inhibitors are administered to horses to prevent endotoxin-induced elaboration of prostaglandins. However, PGE2 and PGI2 stimulate repair of injured intestine. There are 2 isoforms of cyclooxygenase: COX-1, which constitutively produces prostaglandins and COX-2, which is induced by inflammation. We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac, would permit repair as a result of continued COX-1 p...
Santschi EM, Papich MG.The disposition of drugs may differ between pregnant and nonpregnant animals, necessitating a change in dosage. We hypothesized that volume of distribution or clearance may be different for aminoglycoside antibiotics in pregnant mares vs. nonpregnant lactating mares. To examine this hypothesis, we administered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokinetic analysis. The first dose was administered 1-4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1-...
Van Camp SD, Papich MG, Whitacre MD.Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chroma...
Steinman A, Gips M, Lavy E, Sinay I, Soback S.Metronidazole pharmacokinetics in horses was studied after intravenous (i.v.), rectal (p.r.) and oral (p.o.) administration at 20 mg/kg using a triple crossover study design. Metronidazole mean+/-SD half-life was 196+/-39, 212+/-30 and 240+/-65 min after i.v., p.r. and p.o. administration, respectively. The metronidazole clearance was 2.8 (mL/min/kg) and the volume of distribution at steady state was 0.68 L/kg. The pharmacokinetic parameters calculated for metronidazole after administration of the drug by the various routes showed that bioavailability (74+/-18 vs. 30+/-9%) and maximum serum co...
Nieto JE, Snyder JR, Kollias-Baker C, Stanley S.To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. Methods: Jejunal muscle strips from 8 horses. Methods: Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. Results: Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151+/-214 g/cm2 and a molar concentration tha...
Wasfi IA, Abdel Hadi AA, Elghazali M, Boni NS, Alkatheeri NA, Barezaig IM, Al Muharami AM, Hamid AM.The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, ...
French K, Pollitt CC, Pass MA.Experiments were performed to establish the pharmacokinetics of triamcinolone acetonide and the effects of the glucocorticoid on glucose metabolism in horses. The pharmacokinetics after intravenous (i.v.) dosing was best described by a three-compartment open model. There was rapid distribution from the central compartment followed by two phases of elimination. The half-life of the rapid elimination phase was 83.5 min and of the slower phase was 12 h. The term (Vss/Vc)-1was 12.3 indicating extensive distribution into the tissues. Triamcinolone acetonide given i.v. or intramuscularly (i.m. ) ind...
Harkins JD, Robinson NE, Woods WE, Lehner AF, Smith MD, Gates RS, Fisher M, Tobin T.Clenbuterol, a beta2 agonist/antagonist, is the only bronchodilator approved by the US Food and Drug Administration for use in horses. The Association of Racing Commissioners International classifies clenbuterol as a class 3 agent, and, as such, its identification in post-race samples may lead to sanctions. Anecdotal reports suggest that clenbuterol may have been administered by intratracheal (IT) injection to obtain beneficial effects and avoid post-race detection. The objectives of this study were (1) to measure the pharmacological efficacy of IT dose of clenbuterol and (2) to determine the ...
Blackford J, Doherty TJ, Ferslew KE, Panus PC.In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known ...
Aramaki S, Mori M, Nakata M, Shinohara A, Koizumi T.The pharmacokinetics characteristics of propranolol (PPL) in horses was studied by administering the drug intravenously or orally to the animals. The predominant primary pathway was ring oxidation, and 4-hydroxypropranolol glucuronide (4-OHPG) was the major metabolite in both plasma and urine. Side-chain glucuronidation and oxidation were not significant. A two-compartment model was employed for PPL followed by a one-compartment model for 4-OHPG. After oral administration, one-step absorption and two-step first pass metabolism were employed. The fraction absorbed of PPL was approximately 70% a...
Guan F, Uboh CE, Soma LR, Birks EK, Teleis D, Rudy JA, Watson AO, Tsang DS.A reliable and sensitive method for the extraction and quantification of phenytoin (5,5'-diphenylhydantoin), its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) in horse urine and plasma is described. The method involves the use of solid-phase extraction (SPE), liquid-liquid extraction (LLE), enzyme hydrolysis (EH) and high-performance liquid chromatography (HPLC). The minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) was not present in a reliably quantifiable concentration in all samples. The ...
Jouvel C, Maciejewski P, Garcia P, Bonnaire Y, Horning S, Popot MA.A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the ne...
Taylor KC, Vitello LB, Erman JE.The ionization of 4-nitroimidazole to 4-nitroimidazolate was investigated as a function of ionic strength. The apparent pKa varies from 8.99 to 9.50 between 0.001 and 1.0 M ionic strength, respectively, at 25 degrees C. The ionic strength dependence of this ionization is anomalous. The binding of 4-nitroimidazole by horse metmyoglobin was studied between pH 5.0 and 11.5 and as a function of ionic strength between 0.01 and 1.0 M. The association rate constant is pH-dependent, varying from 24 M(-1)s(-1) at pH 5 to a maximum value of 280 M(-1)s(-1) at pH 9.5 and then decreasing to 10 M(-1)s(-1) a...
Plotka ED, Seal US, Eagle TC, Asa CS, Tester JR, Siniff DB.Forty-eight newly captured free-ranging feral stallions (Equus caballus) from two different locations and six captive stallions were immobilized using combinations of etorphine hydrochloride, xylazine hydrochloride and atropine sulfate with or without acepromazine. Six animals were immobilized twice, 1 mo apart. The drugs were administered either intramuscularly (n = 13) or intravenously (n = 44). Mean immobilization time (+/- SE) after intravenous (i.v.) injection of etorphine, xylazine and atropine was 55 +/- 4 sec (range 20 to 185 sec) compared to 708 +/- 131 sec (range 390 to 1,140 sec) fo...
McKiernan BC, Koritz GD, Scott JS, Berney C, Robinson NE.Six ponies with recurrent obstructive lung disease were studied during two separate 60 min periods while receiving constant equal volume infusions of either aminophylline or sterile water. Dynamic lung compliance, pulmonary resistance, respiratory rate, tidal volume, blood gas tensions and heart rate were measured. Plasma samples were obtained for determination of theophylline concentrations before, and at 10 min intervals during, the infusion period. Excitability was assessed subjectively at these same time periods. The plasma theophylline concentrations in ponies were well predicted by a pre...
Derksen FJ, Slocombe RF, Robinson NE.In standing sedated ponies, we measured dynamic lung compliance (Cdyn) and pulmonary resistance (RL) during IV infusion of various doses of histamine; this was done in a given pony 3 times at 1-week intervals between experiments. Histamine doses causing a decrease in Cdyn of 50% and 75% and an increase in RL of 300% and 600% (ED50Cdyn, ED75Cdyn, ED300RL and ED600RL, respectively) were interpolated from the histamine dose-response curves. We also measured respiratory frequency, tidal volume, minute ventilation, functional residual capacity, arterial oxygen tension, arterial carbon dioxide tensi...
Nagata S, Yamashita S, Kurosawa M, Kuwajima M, Hobo S, Katayama Y, Anzai T.To determine the pharmacokinetics and tissue distribution of minocycline in horses. Methods: 5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment. Methods: Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study. Results: No adverse effects were observed in any of the ...
Machin J, Childers T, Kudrimoti S, Eisenberg R, Fenger C, Hartmann P, Maylin G, Shults T, Tobin T.Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemical source by being metabolized in the plant or the horse to aminorex. In Brassicaceae, glucobarbarin is hydrolyzed by myrosinase to yield barbarin, which serves as an insect repellant and/or attractant and is structurally related to aminorex. The synthesis, purification...
Valdez RA, DiPietro JA, Paul AJ, Lock TF, Hungerford LL, Todd KS.The bioequivalence of Strongid C and generic pyrantel tartrate was determined in a controlled study using 30 horses with naturally acquired endoparasitic infections. Three horses were randomly allocated to each of ten replicates based on quantitative nematode and ascarid egg counts and fecal larvae culture results. Horses within each replicate were randomly assigned to one of three treatment groups. Horses in Treatment Group 1 received only oats; horses in Treatment Group 2 received generic pyrantel tartrate pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats; horses in Treatment Group 3 ...
Bertone AL, Jones RL, McIlwraith CW.The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, aft...
Eales FA.Saffan was injected intravenously on 41 occasions in 11 horses and ponies to investigate its possible use in clinical equine anaesthesia. The optimum dose for induction was 1-90 mg per kg. This dose was divided into two halves, the first half given in five seconds and the second half, containing suxamethonium chloride 0.1 mg per kg, in the next 10 seconds. Induction was associated with excitement for up to 30 secs after the assumption of recumbency. At this dose rate anaesthesia lasted five to eight minutes. Muscle relaxation was poor. Recovery was associated with marked tactile and audible hy...
Agne GF, Jung SW, Wooldridge AA, Duran SH, Ravis W, Toribio R.Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics. Objective: To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse. Methods: Six healthy adult mares. Methods: A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharm...
Briant C, Toutain PL, Ottogalli M, Magallon T, Guillaume D.The appropriate dosage regimen for equine FSH (eFSH) (dose, dosing interval) administration in a superovulation treatment in pony mares was determined by a kinetic approach using production rates and kinetic parameters of elimination of the hormone. Two dosage regimens were then tested in superovulation protocols. The eFSH production rates were determined by sampling four ovariectomized pony mares every 10 min for 8 h during the breeding season. Kinetic parameters were determined by administering four dose levels of a preparation of eFSH (4.4, 8.8, 17.6 and 35.2 micro g/kg) by the i.v. route t...
Waraksa E, Owczarek K, Kubica P, Kłodzińska E, Ozimek M, Wrzesień R, Bobrowska-Korczak B, Namieśnik J.Bromhexine (BH), expectorant used in the treatment of respiratory disorders associated with viscid or excessive mucus, is not permitted for use in the competing horse by many authorities in horseracing and Olympic disciplines. Metabolic studies are of the great importance in anti-doping field because they allow for updating the selection of the most appropriate markers for prohibited substances, such as metabolites present at higher concentration levels and/or lasted for a longer period of time in biological samples than a parent drug. This study describes LC-MS/MS-based method for simultaneou...
de Backer P, Vandecasteele-Thienpont LM, Jonckheere JA, Belpaire FM, Debackere M, de Leenheer AP.Bromhexine was administered orally (2 mg./kg.) and intravenously (i. v.) (1 mg./kg.) in 3 horses. Plasma levels were measured and the pharmacokinetic behaviour and bioavailability were estimated. The half-life of elimination after i. v. administration ranged from 3.1 to 4.4 hours. The mean values of the apparent volume of distribution and the volume of distribution of the central compartment amounted to 16.2 and 3.3 1./kg., respectively. A very high plasma clearance, ranging from 49.8 to 59 ml./kg./min., was found.
One hour after oral administration, a mean peak plasma level of about 14 ng....
Manohar M, Goetz TE, Griffin R, Sullivan E.To determine the effects of phenylbutazone administration on heart rate and right atrial and pulmonary vascular pressures in Thoroughbreds during rest and during exercise performed at maximal heart rate. Methods: 7 healthy, exercise-conditioned Thoroughbreds. Methods: Horses were studied on 3 occasions: without medication [control], after i.v. administration of phenylbutazone (4.4 mg/kg of body weight) at 12-hour intervals for 2 days and a final dose given 1 hour before exercise, and after i.v. administration of phenylbutazone for 2 days in the same manner, but with the final dose given 24 hou...
Chapman CB, Courage P, Nielsen IL, Sitaram BR, Huntington PJ.Procaine penicillin is a commonly used antibiotic in equine medicine but its use is associated with a substantial incidence of adverse reactions. Soluble procaine concentrations were determined by HPLC in several commercially available procaine penicillin preparations, including some that were involved in adverse reactions. The mean (+/- SEM) soluble procaine concentrations in the veterinary preparations was 20.18 +/- 5.07 mg/ml, which was higher than the concentration in the only procaine penicillin preparation for use in humans in Australia of 7.3 mg/ml. Heating the veterinary procaine penic...
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...
Van Camp SD, Papich MG, Whitacre MD.Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chroma...
McNeal CD, Ryan CA, Berghaus LJ, Credille BC, Lo CP, Fajt VR.Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidim...
Underwood C, Pollitt CC, Metselaar JM, Laverman P, van Bloois L, van den Hoven JM, Storm G, van Eps AW.Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) coated liposomes were prepared according to the film hydration method and labelled using (99m)Tc-hexamethyl-propylene-amine-oxime. Six horses received 10 g/kg oligofructose via nasogastric tube to induce laminitis, and four control horses received water via nasogastric tube. All horses received 300â...
Tillman LG, Moore JN.The activity of serum angiotensin converting enzyme (ACE) for healthy horses was 64 +/- 13 mUnits/ml. In vitro, equine serum ACE was sensitive to the following inhibitors (IC50): enalapril (570 nM or 215 ng/ml), captopril (190 nM or 41.3 ng/ml), and enalaprilat (6 nM or 2.1 ng/ml). The intravenous (i.v.) administration of angiotensin I to six healthy horses produced a dose proportional pressor response. The maximal increase in mean arterial pressure over baseline values was 65.6 mmHg at angiotensin I doses of 500 ng/kg bodyweight (bwt). The attenuation of this response to angiotensin I was fur...
Symonds NE, Dart AJ, Keledjian J, Lau ML, Ennis LC, McIver VC, Tsang AS, Biasutti SA, Jeffcott LB.To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation. Methods: Experimental using six Standardbred mares. Methods: Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry. Results: Maximum plasma concentrations (t ) were reached by the earliest detection point (...
Xue C, Davis J, Berghaus LJ, Hanafi A, Vaughn SA, Hart KA.Donkeys with clinical signs of pituitary pars intermedia dysfunction are treated with oral pergolide mesylate despite the lack of species-specific pharmacokinetic data. Objective: To evaluate the pharmacokinetics of intragastric and oral pergolide mesylate in healthy donkeys (Equus asinus). Methods: Pharmacokinetic study. Methods: Six healthy donkeys were administered pergolide mesylate (Prascend®) at 2 μg/kg bodyweight (bwt) intragastrically once, then once daily per os (PO) for 5 days. Blood samples were collected at 0, 10, 20, 30 and 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and ...
Salas-Romero J, Gomez-Cabrera K, Molento MB, Lyons ET, Delgado A, González L, Arenal A, Nielsen MK.Equine cyathostomin parasites are ubiquitous in grazing horses and have been shown to cause severe inflammatory disease in the large intestine of horses. Decades of intensive anthelmintic therapy have led to widespread anthelmintic resistance in cyathostomins across the world. In Cuba, no anthelmintic products are formulated and sold for equine usage and little is known about anthelmintic efficacy of ruminant and swine formulations used. A strongyle fecal egg count reduction test was used to assess the efficacy of a liquid formulation of ivermectin labelled for use in swine, ruminants and carn...
Schumacher SA, Toribio RE, Lakritz J, Bertone AL.The objective of this study was to characterize the pharmacokinetics and pharmacodynamics of intravenous administration of magnesium sulfate to horses using a novel radio-telemetry system for physiologic signal capture. Five Horses were surgically implanted with a radio-telemetric carotid catheter. Implants were paired with a non-invasive telemetric unit which acquired a six lead ECG and 3-axis acceleration to assess activity acquired wirelessly in real-time for future analysis. Horses were exposed to a new stall environment before (baseline) and after 60 mg/kg (30 mL) of magnesium sulfate (Mg...
Harkins JD, Lehner A, Karpiesiuk W, Woods WE, Dirikolu L, Boyles J, Carter WG, Tobin T.Bupivacaine is a potent local anaesthetic used in equine medicine. It is also classified as a Class 2 foreign substance by the Association of Racing Commissioners International (ARCI). The identification of residues in postrace urine samples may cause regulators to impose significant penalties. Therefore, an analytical/pharmacological database was developed for this medication. The highest no-effect dose (HNED) for the local anaesthetic effect of bupivacaine was determined to be 0.25 mg by using an abaxial sesamoid local anaesthetic model. Administration of the HNED of bupivacaine to eight hor...
Paine SW, Harding C, Waller CC, Zemenova J, Viljanto M, Habershon Butcher J, Hincks PR.Calcium dobesilate (CD) is a synthetic venoactive drug used in veterinary medicine to treat equine navicular disease. Etamsylate is a haemostatic agent used in horses for the treatment of exercise-induced pulmonary haemorrhage. Both etamsylate and CD dissociate in the circulatory system with 2,5-HBSA as the active drug. The aim of the research was to be able to provide detection time (DT) advice from pharmacokinetic (PK) studies in Thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Two (pilot stud...
Oku K, Ohta M, Yamanaka T, Mizuno Y, Fujinaga T.To investigate an adequate infusion rate of propofol for total intravenous anesthesia (TIVA) in horses, the minimum infusion rate (MIR) comparable to the minimum alveolar anesthetic concentration (MAC) of inhalation anesthetic was determined under constant ventilation condition by intermittent positive pressure ventilation (IPPV). In addition, arterial propofol concentration was measured to determine the concentration corresponding to the MIR (concentration preventing reaction to stimulus in 50% of population, Cp(50)). Further, 95% effective dose (ED(95)) was estimated as infusion rate for acq...
Kuroda T, Minamijima Y, Mita H, Tamura N, Fukuda K, Kuwano A, Toutain PL, Sato F.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5Â mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC-MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10Â mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by M...
Magdesian KG, Wilson WD, Mihalyi J.To determine disposition kinetics of amikacin in neonatal foals administered high doses at extended intervals. Methods: 7 neonatal foals. Methods: Amikacin was administered (21 mg/kg, i.v., q 24 h) for 10 days. On days 1, 5, and 10, serial plasma samples were obtained for measurement of amikacin concentrations and determination of pharmacokinetics. Results: Mean +/- SD peak plasma concentrations of amikacin extrapolated to time 0 were 103.1 +/- 23.4, 102.9 +/- 9.8, and 120.7 +/- 17.9 microg/mL on days 1, 5, and 10, respectively. Plasma concentrations at 1 hour were 37.5 +/- 6.7, 32.9 +/- 2.6, ...
Tobin T, Harkins JD, Sams RA.Proper veterinary care of horses requires that horses in training have access to modern therapeutic medication. However, the sensitivity of equine drug testing now allows for detection of pharmacologically insignificant concentrations of many therapeutic medications. In 1995, the Association of Racing Commissioners International (ARCI) resolved that members 'address trace level detection so as not to lead to disciplinary action based on pharmacologically insignificant traces of these substances'. The rationale behind this approach is to prevent overly-sensitive testing from inhibiting the prop...
Uboh CE, Rudy JA, Soma LR, Fennell M, May L, Sams R, Railing FA, Shellenberger J, Kahler M.The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in...
