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.
Miyamoto A, Obi T, Nishio A.The vasomotor effects of 5-hydroxytryptamine (5-HT) on isolated equine basilar arteries were studied. 5-HT induced contractions of equine basilar arteries in a concentration-dependent manner, with a pEC50 value (with 95% confidence limits) of 7.35 (7.08-7.62). Similar results were obtained with endothelium-denuded basilar arteries. Contractions were not competitively inhibited by the 5-HT2 receptor antagonist ketanserin at low concentrations of 5-HT. Conversely, at high concentrations of 5-HT, contractions were inhibited by ketanserin in a concentration-dependent manner, with a pA2 value of 8....
Simonsen U, Prieto D, Sánez de Tejada I, García-Sacristán A.1. The involvement of nitric oxide (NO) and the signal transduction mechanisms mediating neurogenic relaxations were investigated in deep intracavernous penile arteries with an internal lumen diameter of 600-900 microns, isolated from the corpus cavernosum of young horses. 2. The presence of nitric oxide synthase (NOS)-positive nerves was examined in cross and longitudinal sections of isolated penile arteries processed for NADPH-diaphorase (NADPH-d) histochemistry. NADPH-d-positive nerve fibres were observed in the adventitia-media junction of deep penile arteries and in relation to the trabec...
Swan GE, Guthrie AJ, Mülders MS, Killeen VM, Nurton JP, Short CR, van den Berg JS.The pharmacokinetics of gentamicin following single and multiple intravenous and intramuscular doses were compared in a two phase, randomised cross-over study in horses. Gentamicin was administered to 6 healthy, conditioned Thoroughbred mares at a dosage of 3.3 mg/kg body weight every 12 hours for 5 intravenous or intramuscular consecutive treatments. Equal numbers of horses were treated by either route during each phase. There was a wash-out period of 5 days between phases. During each phase serial blood samples were collected from each mare immediately before treatment and at 16 intervals fo...
Hinchcliff KW, McKeever KH, Muir WW, Sams RA.The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg, PO, at 24 hours and 4.4 mg/kg, IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration si...
Elliott J, Soydan J.Isolated equine digital veins (EDVs) were used to study beta-adrenoceptor mediated vasodilation and to examine isoxsuprine's vasodilatory mechanism of action. When the blood vessel wall tension was raised with potassium chloride solution (KCl; 59 mmol/l), the order of vasodilator potency of beta-agonists was: isoprenaline > fenoterol > noradrenaline > dobutamine > isoxsuprine. The beta 2-selective adrenoceptor antagonist, ICI 118551 (1 nmol/l) caused a 6.74 and 6.65-fold parallel shift to the right in the dose response curves to fenoterol and noradrenaline respectively. Propranolol...
Soma LR, Uboh CE, Rudy JA, Perkowski SZ.Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after IV administration in horses. The plasma disposition, after IV administration of 5 mg/kg of body weight, was described by a two-compartment model; mean +/- SD distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56 hours, respectively. Plasma concentration of naproxen...
McCann ME, Watson TD, Boudinot FD, Moore JN.We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination...
Dillon AM, Heath MF.The effects of the protein tyrosine kinase inhibitors tyrphostins B42 and B46 on equine platelet function and protein tyrosine phosphorylation (PTP) were assessed. Tyrphostins B42 and B46 (both at 100 microM concentration) produced significant inhibition of thrombin-stimulated equine platelet aggregation. The effect of tyrphostin B46 was also time-dependent. The same concentration of these inhibitors produced very little or no inhibition of platelet-activating factor (PAF)-induced aggregation. The effects of tyrphostins B42 and B46 on thrombin- and PAF-stimulated PTP were generally similar, al...
Landoni MF, Lees P.A comparative study in horses of the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 extensively used nonsteroidal anti-inflammatory drugs (NSAIDs), flunixin (FXN) and ketoprofen (KTP), was carried out applying PK/PD modelling. To evaluate the anti-inflammatory properties of these drugs a model of acute inflammation, comprising surgically implanted subcutaneous tissue cages stimulated by intracaveal injection of carrageenan, was used. FXN elimination half-life (T1/2 beta) in plasma was 3.37 +/- 1.09 h. However, in exudate a much longer T1/2 beta was obtained (15.99 +/- 3.80 h). Apparent v...
el-Komy AA.The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [...
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
Koupai-Abyazani MR, Yu N, Esaw B, Laviolette B.Urine and serum samples collected from four standard-bred mares after 30-mg intraarticular administrations of triamcinolone acetonide were analyzed using combined high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry. Maximum triamcinolone acetonide concentrations of 32.3, 14.8, 24.3, and 29.4 ng/mL in the urine and 2.7, 1.9, 2.3, and 2.5 ng/mL in the serum samples were observed. The peak concentrations of the drug were detected approximately 22 h (urine) and 12 h (serum) after administration. The drug elimination profiles for both urine and serum are present...
Rossier Y, Divers TJ, Sweeney RW.The urinary GGT/urinary creatinine (uGGT/uCR) ratio was measured on Days 1, 3 and 10 in 4 adult, healthy horses; in 6 adult, healthy horses treated with gentamicin at recommended dosages and 9 adult horses treated for pleuropneumonia with gentamicin at recommended dosages. Plasma creatinine and gentamicin trough concentrations were measured on the same days. The uGGT/uCr ratio was higher in the normal horses (mean +/- s.d. 22.85 +/- 13.69) than previously reported normal values (10.5 +/- 6.8) (Adams and McClure 1985). Analysis of variance for repeated measures was used to compare the ratio in ...
Soraci A, Benoit E, Jaussaud P, Lees P, Delatour P.Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours afte...
Reef VB, Reimer JM, Spencer PA.Forty-one horses were treated for atrial fibrillation (AF) with 22 mg/kg quinidine sulfate via nasogastric tube every 2 hours until conversion to sinus rhythm, a cumulative dose of 88 to 132 mg/kg had been administered in 2-hour increments, or the horse had adverse or toxic effects from the drug. Treatment intervals were prolonged to every 6 hours if conversion had not occurred. Digoxin was administered before treatment if the horse had a fractional shortening < or = 27% (3 horses), was prone to tachycardia (resting heart rate > or = 60 beats/min) (1 horse), or had a previous history of sustai...
Fey K, Klatt P, Schmidt H, Sasse HH.Five healthy horses were given a sulfadoxine/trimethoprim combination (Borgal, Hoechst AG) i.v. on day 1. The next ten days the horses got once a day a sulfadimethoxine/trimethoprim combination orally (Trafigal, Hoechst AG). The doses were given as recommended. One horse received no medicaments for control. On each horse six bronchoalveolar lavages were performed. Blood samples were taken to calculate blood levels and elimination half lives. To determine the amount of substances in lavage fluid and plasma the high performance liquid chromatography (HPLC) was used. Regularly low quantities of s...
Gronert GA, Fung DL, Jones JH, Shafer SL, Hildebrand SV, Disbrow EA.We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmaco...
Roncada P, Tomasi L, Montesissa C, Grossi G, Stracciari GL, Anfossi P.The kinetics of 2 formulations of theophylline were studied in horses. In an initial cross-over study (Phase I) serum concentration-time curves were determined for granulated and microencapsulated theophylline after a single oral administration (5 mg/kg bwt). In Phase II microencapsulated theophylline was administered at 5 mg/kg bwt/12 h for 10 days at feeding time, as in normal clinical practice. Although no significant differences between the 2 preparations were found with respect to the main kinetic parameters, the microencapsulated form was more evenly and completely absorbed from the dige...
Toutain PL, Autefage A, Legrand C, Alvinerie M.The purpose of the present study was to establish in the horse the relationship between plasma concentration profiles of phenylbutazone (PBZ) and flunixin meglumine (FM) and their pharmacological effects in order to build a predictive pharmacokinetic/pharmacodynamic (PK/PD) model. In five horses, an experimental arthritis was induced by injecting Freund's adjuvant into a carpal joint. PBZ (4 mg/kg) and FM (1 mg/kg) were injected by the intravenous route as a single intravenous dose in two different trials. Five pharmacodynamic end-points were regularly measured after test article injection usi...
Kamerling SG, Owens JG.The actions of most drugs are dependent upon achieving adequate plasma concentrations. Plasma concentrations are influenced by the degree to which a drug is absorbed, distributed, metabolized and excreted. Pharmacokinetic assessment reflects changes in these variables as a function of time. Pharmacodynamics refers to specific drug effects or mechanisms of drug action. Individual drug pharmacokinetics provides information on which to base a therapeutic dose, route of administration and dosing interval. However, not all drug actions temporally correlate with plasma kinetics. To resolve this disc...
Hardy J, Bednarski RM, Biller DS.Pharmacologically induced splenic contraction might be useful during certain medical or surgical procedures in horses. The effects of phenylephrine, an alpha 1-adrenergic receptor agonist, on hemodynamic function and splenic dimensions were examined in 6 healthy adult horses. Phenylephrine infusion (1, 3, or 6 micrograms/kg of body weight/min for 15 minutes) resulted in a dose-related increase in mean pulmonary artery pressure; right atrial pressure; systolic, mean, and diastolic arterial pressures; and packed cell volume (P = 0.0001). Concurrent decreases in heart rate and specific cardiac ou...
Delbeke FT, Landuyt J, Debackere M.Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal conc...
Marroum PJ, Webb AI, Aeschbacher G, Curry SH.A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pat...
Young DB, Ewing PJ, Burrows GE, Lessley BA, Clarke CR, Shawley RV.Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 8.8 mg/kg i.v. phenylbutazone; and 1...
Heath MF, Evans RJ, Poole AW, Hayes LJ, McEvoy RJ, Littler RM.The responses of equine blood platelets in citrated platelet-rich plasma to arachidonic acid, U44069 (prostaglandin endoperoxide analogue), adenosine 5'-diphosphate, platelet-activating factor or collagen were investigated by turbidimetric aggregometry. Pre-treatment of the platelets with aspirin (1 mmol/l) or paracetamol (1.3 mmol/l) abolished shape change and aggregation in response to arachidonic acid; decreased the rate of aggregation in response to collagen, with no separate effect on shape change; had no marked effect on aggregation caused by the other agonists; but in no case transforme...
Ellis EJ, Ravis WR, Malloy M, Duran SH, Smyth BG.Six horses were administered either 15 or 20 mg/kg body weight (b.w.) procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasma concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA plasma concentrations could be described by a one-compartment model with a t1/2 of 3.49 +/- 0.61 h. The total body clearance of PA was 0.395 +/- 0.090 l/hr/kg and the volume of distribution was 1.93 +/- 0.27 l/kg. As observed after PA administration, NAPA (an active metabolite) had a t1/2 longer than PA of 6....
Boone L, Schumacher J, DeGraves F, Cole R.The objective of this study was to determine if buffering mepivacaine HCL (mepHCl) with sodium bicarbonate (NaHCO3) would significantly decrease the time to onset of analgesia when performing median and ulnar nerve blocks in naturally lame horses. Median and ulnar nerve blocks were performed on the naturally lame limb of nine horses during two separate study periods, with a minimum washout period of three days between study periods. Nerve blocks were performed by administering mepHCl alone or mepHCl mixed with NaHCO3 (nine parts 2 per cent mepHCl to one part 8.4 per cent NaHCO3). Lameness was ...
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...
Recio P, López PG, Fernández JL, Garcia-Sacristán A.1. The presence and types of alpha and beta-adrenoceptors in the corpus cavernosum of the horse were studied in vitro by using selected ligands of adrenoceptors and isometric tension recording. 2. Noradrenaline and phenylephrine induced concentration-dependent contractions in corpus cavernosum preparations. B-HT 920 had no effect. 3. Phentolamine and prazosin produced a shift to the right of the dose-response curve of noradrenaline, while the alpha(2)-antagonist, rauwolscine had no effect on the response to noradrenaline. Phenylephrine-evoked contractions of corporal strips were significantly ...
Bishop RC, Wilkins PA, Kemper AM, Stewart RM, McCoy AM.Nonsteroidal anti-inflammatory drug (NSAID) administration carries risks of gastrointestinal toxicity. Selective COX-2 inhibitors ("coxibs") were designed to reduce risks of adverse effects but are still associated with gastrointestinal complications in humans. The effect of coxibs on colonic inflammation and integrity in horses is unknown. The study objective was to compare the effects of the coxib firocoxib and the nonselective NSAID flunixin meglumine on ultrasonographic indicators of colonic inflammation in healthy horses. Twelve healthy adult horses were administered flunixin meglumine (1...
Schutzer WE, Kerby JL, Holtan DW.Trilostane, a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, was administered intravenously to pregnant mares (n = 3) between day 277 and day 282 of gestation to determine its effect on the progestin milieu. In addition, placental tissue from mares at mid-gestation (150-300 days) (n = 4) were exposed to either deuterium-labelled pregnenolone alone or deuterium-labelled pregnenolone and trilostane to examine the effect of trilostane on placental metabolism of pregnenolone. Blood samples were collected from indwelling jugular catheters at frequent intervals for 48 h after infusion...
Ohmura H, Hiraga A, Aida H, Takahashi T, Nukada T.To determine oral dosage and to evaluate the pharmacokinetics in horses of orally administered flecainide, an antiarrhythmic drug, the correlations between its plasma concentration and PR, QRS and QT intervals in equine electrocardiograms (ECG) were investigated. Six healthy horses were administered a randomly ordered dose of 4 or 6 mg/kg of flecainide acetate. The ECG was monitored (heart rate (HR), PR, QRS, and QT intervals) and blood was taken at timed intervals to measure the plasma flecainide concentrations pre- and post-administration. The maximum plasma concentration reached 1014+/-285 ...
Lees P, Higgins AJ, Mawhinney IC, Reid DS.The absorption pattern of phenylbutazone was studied in five horses during administration of the drug in a paste formulation on days 1, 5, 8 and 12 of a 12-day dosing schedule. Since two or more plasma concentration peaks were usually obtained following each oral dose, it was concluded that phasic absorption was a particular feature of the oil:water formulation of the product. Possible causes of this unusual absorption pattern are discussed and the therapeutic implications of both phasic absorption and the recorded values of Cmax, tmax and AUC024 for phenylbutazone and its active metabolite ox...
Kaegi B.25 horses which entered the clinic for minor surgery, received ketamine (2.2 mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v. (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a benzodiazepine antagonist, was injected at a dose of 0....
Knych HK, Kanarr K, Fang Y, McKemie DS, Kass PH.To describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses. Methods: Randomized balanced crossover study. Methods: A total of seven University-owned horses, five mares and two geldings, aged 3-6 years. Methods: Horses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg), M6G (0.01 mg kg) and M3G (0.03 mg kg). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentr...
Lees P, Taylor JB, Maitho TE, Millar JD, Higgins AJ.The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.13h-1, t1/2 beta = 5.46h, Vdarea = 0.141 1/kg and C1B = 17.9 ml/kg/h. The hydroxylated metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbuta...
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 ...
Kohn CW, Sams R, Kowalski JJ, Powers J, Wallace S.The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin i...
Swanson CR, Muir WW.The influence of pharmacologic enhancement of cardiac output on the alveolar-to-arterial oxygen tension (difference (P[A-a]O2), physiologic right-to-left shunt fraction (Qs/Qt), and physiologic dead space-to-tidal volume ratio (VD/VT) ws studied in halothane-anesthetized horses in left lateral, right lateral, and dorsal recumbencies. Adult horses were anesthetized, using xylazine (2.2 mg/kg, IM), guaifenesin (50 mg/kg, IV), thiamylal (4.4 mg/kg, IV), and halothane (1.5% to 2% inspired) in 100% O2. Mechanical ventilation was controlled to maintain arterial eucapnia (PaCO2) 35 to 45 mm of Hg) fo...
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...
Hanafi AL, Reed RA, Trenholme HN, Sakai DM, Ryan CA, Barletta M, Quandt JE, Knych HK.To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Methods: prospective, randomized, blinded, crossover trial. Methods: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were c...
Frost AB, Larsen F, Larsen SW, Østergaard J, Thomsen MH, Stürup S, Andersen PH, Larsen C.To establish a pharmacokinetic model for the model drug, sodium diatrizoate (DTZ), allowing joint disappearance kinetics to be estimated from serum appearance kinetics following intra-articular administration, and to calculate the relative joint exposure after intravenous and intra-articular DTZ administration (F(iv/IA)). Methods: Each of five horses received an aqueous solution of 3.9 mg/kg sodium diatrizoate both intravenously and intra-articularly separated by a one-week wash out period. Serum and synovial samples were collected over 7 h and analyzed for content of model compound using indu...
Norman WM, Court MH, Greenblatt DJ.To evaluate changes in the pharmacokinetic disposition of diazepam in foals from 4 to 84 days of age. Methods: 4 male and 2 female full-term mixed-breed foals. Methods: Diazepam terminal half-life, volume of distribution, clearance, free fraction, unbound volume of distribution, free clearance, peak desmethyldiazepam concentration, and area under the desmethyldiazepam concentration-time curve were determined after i.v. administration of 0.25 mg of diazepam/kg of body weight to foals at 4, 21, 42, and 84 days of age. Results: Disposition of diazepam was best described using a two-compartment mo...
Lippert-Gruner M, Svestkova O.The acute management of spasticity following ABI is challenging. Contractures can occur during the acute phases of illness. The joints most affected are the shoulders and the ankles. Methods: A case study of a 48-year-old female patient who received local chemoneurolytic anti-spasticity therapy following a severe subarachnoid haemorrhage for pes equines deformity is presented to illustrate the role of focal neurotoxin therapy. Methods: The increasing spasticity in her legs was observed and could not be effectively treated with oral anti-spasticity agents or intensive physiotherapy. As spastici...
Wood T, Weckman T, Woods WE, Tobin T, Dougherty J.Variable interval (VI) reinforcement scheduling is a specific type of operant conditioning that is sensitive to drug effects even when overt clinical signs of the drug have diminished. Six horses were conditioned to break a light beam with a head-bobbing movement and this behaviour was reinforced with a reward of clean oats (approximately 30 mg/reinforcement). Initial training procedures included familiarisation with the behavioural equipment and fixed-ratio reinforced scheduling. To establish baseline rates of behaviour, the horses were converted to a variable interval (60 secs) reinforcement...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Sutton GA, Kelmer G. The aim of this study was to determine the time (T) to the maximum concentration (C) of amikacin sulphate in synovial fluid of the radiocarpal joint (RCJ) following cephalic intravenous regional limb perfusion (IVRLP) using 2 g of amikacin sulphate. Methods: Cephalic IVRLP was performed with 2 g of amikacin sulphate diluted in 0.9% NaCl to a total volume of 100 mL in six healthy adult mixed breed mares. An Esmarch's rubber tourniquet was applied for 30 minutes and the antibiotic solution was infused through a 23-gauge butterfly catheter. Synovial fluid was collected from the RCJ ...
Easton S, Pinchbeck GL, Bartley DJ, Hotchkiss E, Hodgkinson JE, Matthews JB.The aim of this study was to determine practices, attitudes and experiences of UK prescribers of anthelmintics for horses and livestock. A questionnaire was sent by direct email to groups licenced to prescribe these medicines. These were veterinarians, Suitably Qualified Persons (SQPs, registered with the Animal Medicines Training Regulatory Authority) and veterinary pharmacists. The survey was also advertised through social media. It comprised questions relating to demographics, training experiences, current prescribing practices, as well as personal opinions on anthelmintic selection, diagno...
Raekallio M, Vainio O, Karjalainen J.Detomidine (10 micrograms/kg and 20 micrograms/kg) was administered to seven horses with and without epinephrine infusion (0.1 microgram/kg/min) from 5 minutes before to 5 minutes after detomidine injection. One or more single supraventricular premature heartbeats were observed in three horses after detomidine administration. Epinephrine infusion did not modify the incidence of cardiac arrhythmias in detomidine-treated horses at the doses tested. Relatively high momentary peak systolic pressures were registered in some horses after detomidine administration during epinephrine infusion. The hig...
Abo El Sooud K.The pharmacokinetics of gentamicin was studied in lambs, calves and foals, respectively after single intravenous (i.v.) injections of 5 mg kg(-1) body weight. The plasma concentration-time curves of gentamicin sulphate were best fitted to follow a two-compartment open model in calves and foals and a three-compartment open model in lambs. Gentamicin showed high plasma level at 5 min post-injection. Then its concentration decreased gradually until its minimum detectable level at 10 and 12 h post-injection in foals and calves, respectively, was reached. In contrast, the plasma concentrations were...
Hinchcliff KW, McKeever KH, Muir WW, Sams RA.The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg, PO, at 24 hours and 4.4 mg/kg, IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration si...
Rubie S, Robinson NE, Stoll M, Broadstone RV, Derksen FJ.Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg ...
Spensley MS, Baggot JD, Wilson WD, Hietala SK, Mihalyi JE.Plasma and endometrial tissue concentrations of ticarcillin were measured in healthy mares. In the first of the 3 separate phases comprising the study, ticarcillin disodium (30 mg/kg) was administered IV. The mean peak concentration in endometrial tissue, 12.9 micrograms/g, was attained at 30 minutes. The plasma half-life of the drug in the 6 mares was 0.83 +/- 0.22 hour. Six grams of the drug was diluted in 250 ml of sodium chloride injection USP (2nd phase) and in 60 ml of sodium chloride injection USP (3rd phase). These dilutions were administered by intrauterine infusion. In phase 2, the m...
Kuroda T, Nagata SI, Tamura N, Mita H, Kusano K, Mizobe F, Takizawa Y, Fukuda K, Kasashima Y.To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube. Methods: 4 healthy adult Thoroughbreds. Methods: Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios we...
Frias AF, Mársico F, Gómez de Segura IA, Nascimento PR, Nascimento A, Soares JH, Almosny NR.To characterize responses to different doses of propofol in horses pre-medicated with xylazine. Methods: Six adult horses (five females and one male). Methods: Each horse was anaesthetized four times with either ketamine or propofol in random order at 1-week intervals. Horses were pre-medicated with xylazine (1.1 mg kg-1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg-1 IV) or propofol (1, 2 and 4 mg kg-1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 1...
Dyke TM, Hinchcliff KW, Sams RA.The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide...
Stevenson AJ, Weber MP, Todi F, Young L, Beaumier P, Kacew S.Plasma and urinary concentrations of procaine were examined in Standardbred mares after subcutaneous administration of various doses (80 mg to 1600 mg) of procaine hydrochloride. Regardless of dose, peak plasma procaine values occurred within 1 h, but remained detectable in a dose-dependent manner, with procaine present at 1 h with the 80 mg dose and 6 h at the 1600 mg dose. Similarly, peak urinary procaine concentrations were attained within 1.5 to 3 h, irrespective of dose, while detection time was dose-dependent, being 23 h for 80-200 mg doses but as long as 30-54 h with the 1600 mg dose. W...
