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.
Hague BA, Martinez EA, Hartsfield SM.To evaluate effects of a single high dose of gentamicin on neuromuscular function in horses anesthetized with halothane. Methods: 6 healthy adult horses. Methods: Halothane-anesthetized horses were positioned in left lateral recumbency, and the right hind limb was immobilized in a reusable fiberglass cast fixed to a steel frame. The hoof was attached to a force transducer, and resting tension of 0.93 +/- 0.16 kg was maintained. A supramaximal train-of-four stimulus of 2 Hz for a duration of 0.25 millisecond was applied to the superficial peroneal nerve every 20 seconds by a square-wave stimula...
Harkins JD, Queiroz-Neto A, Mundy GD, West D, Tobin T.This report describes the development of a behaviour chamber and the validation of the chamber of measure locomotor activity of a horse. Locomotor activity was detected by four Mini-beam sensors and recorded on a data logger every 5 min for 22 h. Horses were more active during daytime than in the evening, which was at least partially related to human activity in their surroundings. To validate the ability of the chambers to detect changes in activity, fentanyl citrate and xylazine HCl, agents well-characterized as a stimulant and a depressant, respectively, were administered to five horses. Fe...
Luukkanen L, Katila T, Koskinen E.Detomidine was given to 11 pregnant mares at 3 week intervals during the last trimester of pregnancy. Maternal and fetal electrocardiographs were recorded and fetal activity studied by transabdominal ultrasonography, before and 2 h (2, 5, 10, 20, 30, 60, 90 and 120 min) after injection. After parturition, the foals were examined and weighed. Maternal and fetal heart rate showed an initial decline after detomidine administration. Maternal heart rate in the treatment group were lower already 2 min after injection, but a reduction in fetal heart was first seen 5 min after detomidine administratio...
Doherty TJ, Geiser DR, Rohrbach BW.The effect of i.v. acepromazine (0.05 mg/kg bwt), butorphanol (0.05 mg/kg bwt) and a combination of acepromazine and butorphanol on halothane minimum alveolar concentration (MAC) was determined in 7 mixed-breed ponies. Ventilation was controlled, and blood pressure and temperature were maintained within normal limits. Following the determination of baseline MAC, treatments were administered to each pony in a random manner. The control treatment was normal saline. The baseline halothane dMAC for the control group was 0.91 +/- 0.04%, and no significant change occurred after saline administration...
Kaartinen L, Panu S, Pyörälä S.Pharmacokinetic behaviour of enrofloxacin was studied in 6 horses after intravenous (i.v.) or intramuscular (i.m.) administration of enrofloxacin (5 mg/kg bwt). Concentration of enrofloxacin and ciproflaxin were measured by high performance liquid chromatography in serum. Antimicrobial activity of the samples was determined with an agar-diffusion technique. Reactions at the site of i.m. injection were monitored clinically and by determination of serum creatine kinase (CK) activity. After i.v. administration, elimination half-life of enrofloxacin was 4.4 h and volume of distribution was 2.3 1/k...
Easter JL, Hague BA, Brumbaugh GW, Nguyen J, Chaffin MK, Honnas CM, Kemper DL.To evaluate the effect of peritoneal lavage on pharmacokinetics of gentamicin sulfate in healthy horses after experimental celiotomy. Methods: 13 clinically normal horses. Methods: Horses were randomly assigned to control or experimental groups. All horses received gentamicin (6.6 mg/kg of body weight, IV, q 24 h) before surgery, underwent experimental abdominal surgery, and had abdominal drains placed percutaneously. Horses of the experimental group received postoperative peritoneal lavage; horses of the control group did not receive peritoneal lavage. The day after surgery, 24 hours after th...
Duvivier DH, Votion D, Vandenput S, Art T, Lekeux P.To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function w...
Elliott J.Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha2-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha1-adreno...
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...
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...
van Nieuwstadt RA, Henricks PA, Hajer R, van der Meer van Roomen WA, Breukink HJ, Nijkamp FP.This study was undertaken to assess the importance of muscarinic receptor subtypes in equine airway disease. Smooth muscle strips from the mid-cervical portion of the trachea of horses were placed in tissue baths and isometric contractile force was measured. Active force was measured in response to metacholine and the selective muscarinic receptor agonists McN-A-343 (M1-selective) and pilocarpine (M2-selective) in cumulative concentrations (10(-9)M through 10(-3)M), with and without preincubation with three or four concentrations of the selective muscarinic receptor antagonists pirenzepine (M1...
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 ...
Anfossi P, Villa R, Montesissa C, Carli S.Lysine salts are often used in human pharmaceuticals to increase the solubility and absorption of acidic drugs when these are administered parenterally. In this study the intramuscular bioavailability of ketoprofen administered as the lysine salt was evaluated in horses (n = 5) treated intravenously and intramuscularly (2.2 mg/kg active substance) in a cross-over study. The absorption rate of ketoprofen administered as the lysine salt was rather low: the mean residence time increased from 31.7 min after IV injection to 128.9 min (after IM injection), and the bioavailability was high (mean 92.4...
Young LE, Blissitt KJ, Clutton RE, Molony V.To evaluate the hemodynamic effects of a 60-minute infusion of dopexamine in horses anesthetized with halothane. Methods: 7 adult Thoroughbreds. Methods: Measurements of left ventricular function obtained by transesophageal Doppler echocardiography and cardiac catheterization. Results: Infusion of dopexamine (4 micrograms/kg of body weight/min) significantly increased heart rate, cardiac output, maximal rates of increase and decrease of left ventricular pressure, and maximal acceleration and maximal velocity of aortic blood flow. Left ventricular ejection time significantly increased, and pre-...
Simonsen U, Prieto D, Hernández M, Sáenz de Tejada I, García-Sacristán A.The receptors mediating the contractions to both exogenously applied noradrenaline and electrical field stimulation (EFS) were characterized in horse isolated penile resistance arteries. The alpha 1-adrenoceptor-selective antagonist, prazosin, caused competitive rightward shifts of the contractile concentration-response curves (CRC) to phenylephrine. The alpha 2-antagonist, rauwolscine, also displaced to the right the CRC to the alpha 2-adrenoceptor-selective agonist, BHT 920. EFS (0.3 ms, 20-second trains) caused tetrodotoxin-sensitive frequency-dependent contractions which were enhanced in t...
Johnson CB, Taylor PM.Opioids have variable effects on the minimum alveolar concentration of inhaled anaesthetics in the horse. During halothane anaesthesia at an end-tidal halothane concentration between 0.75 and 0.85 percent, the electroencephalogram (EEG) frequency power spectrum and the auditory evoked potential were recorded continuously in eight ponies during an infusion of approximately 40 micrograms kg-1 alfentanil over five minutes, and for a further 55 minutes. The spectral edge and median frequency of the EEG and the mid-latency of the auditory evoked potential at the time of maximum change of these vari...
Flaherty D, Reid J, Welsh E, Monteiro AM, Lerche P, Nolan A.The pharmacodynamics of infusions of propofol alone (group 1) were compared with the pharmacodynamics of infusions of propofol and ketamine together (group 2) in eight ponies undergoing castration. Anaesthesia was induced with detomidine, 20 micrograms kg-1, followed by ketamine, 2.2 mg kg-1. Subsequently, a bolus dose of propofol, 0.5 mg kg-1, was administered intravenously to both groups, and an infusion of propofol was given for an average of 74 minutes to group 1, and an infusion of propofol and ketamine was given for 60 minutes to group 2. The mean (SD) infusion rates of propofol were 0.3...
Young SS, Tesarowski D, Viel L.The effect of measurement frequency on respiratory mechanics was investigated in six horses with reversible allergic airway disease. Total respiratory impedance was measured at 1.5, 2.0, 3.0, and 5.0 Hz by using the forced oscillation technique with the horses in remission, after acute antigenic challenge producing clinical heaves, and with heaves but after the administration of 2 mg fenoterol by inhalation. The slopes of the magnitude (magnitude of Zrs) and real part (R) of total respiratory impedance over the frequency range 1.5-3 Hz changed significantly after antigenic challenge and fenote...
Landoni MF, Lees P.Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three-period cross-over study using a tissue cage model of inflammation. For both S(+)-and R(-)-KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degre...
Crisman MV, Wilcke JR, Sams RA.To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals < 24 hours old. Methods: 6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours). Methods: Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by j...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Ensink JM, Klein WR, Barneveld A, Vulto AG, Van Miert AS, Tukker JJ.The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. ...
England GC, Clarke KW.In recent years the usefulness of the alpha 2 adrenoceptor agonist drugs has been recognized in equine practice. Several agents have become available and are now licensed for use in a number of countries. The principle actions of all alpha 2 adrenoceptor agonists are similar, in that they produce a reduction in heart rate and alteration of heart rhythm, an initial hypertension followed by a prolonged hypotension, a decrease in the cardiac output and respiratory depression. For clinical purposes, these agents produce sedation and analgesia, they are useful for premedication and markedly potenti...
Yamashita K, Yonezawa K, Izumisawa Y, Kotani T.The antagonistic effects of atipamezole (20, 40, 60, 80, and 100 micrograms/kg i.v.) on medetomidine (10 micrograms/kg i.v.)-induced sedation were evaluated in horses. Although 20 and 40 micrograms/kg of atipamezole were not sufficient to reverse the sedation, 60 micrograms/kg did effectively reverse the sedation. Atipamezole at 80 micrograms/kg was more potent, and significantly shortened the duration of sedation without any apparent side effects, but a higher dose of 100 micrograms/kg was not more effective than 80 micrograms/kg. The possible use of atipamezole as a reversal agent may enhanc...
Corveleyn S, Deprez P, Van der Weken G, Baeyens W, Remon JP.Six healthy mares ranging in age from 6 to 12 years and weighing from 415 to 540 kg were used to determine the rectal bioavailability of ketoprofen. For the rectal administration, three different formulations, each containing 1 g of ketoprofen, were administered in a fatty and a hydrophilic suppository base and as a liquid suspension. An average elimination half-life of 1.3 h (+/-1.2) was found. The average value for the total plasma clearance (ClT) was 131.9mL/ min.kg (range 95-183.5). The volume of distribution Vd(area) was 255 mL/kg and the mean residence time (MRT) value was 0.47 h. After ...
Delatour P, Garnier F, Maire R.After administration of the racemic drug, the stereoselective quantification of the enantiomers of free and conjugated carprofen was performed in human plasma and in plasma, urine and bile of dogs and horses. In humans, the plasma profile of free carprofen and its glucuronides is not stereoselective and the glucuronides excreted in urine are close to a racemate. In dogs and horses on the contrary, the R(-) enantiomer of the free drug is predominant in plasma, while urine and/or bile concentrations of the glucuronides are high in comparison to plasma with a strong selectivity for the S(+) enant...
Klee S, Nürnberger MC, Keller H, Ungemach FR.A therapeutical dose of kanamycin was tested intravenously and intramuscularly in four normal standardbreds and plasma concentrations were measured over a 12 hour period. Plasma levels exceeded a minimum inhibitory concentration of 4 micrograms/ml within only 15 minutes for 8 hours both after i.v. and i.m. injection. Kanamycin revealed a mean plasma half life of 2.3 hours. Bioavailability of an intramuscular dose was about 76%. The pharmacokinetic parameters demonstrate the rapid onset of antibacterial plasma levels of the test compound. A dose regimen for horses of two times daily 5 mg/kg bod...
Todhunter RJ, Fubini SL, Wootton JA, Lust G.The effect of different doses of methylprednisolone acetate (MPA) on proteoglycan and collagen metabolism of articular cartilage from normal equine joints was tested in vitro. Methods: Cultured explants were treated with 0, 0.0004, 0.004, 0.04, 0.4 and 4.0 mg/ml (approximately 10(-6)-10(-2) M) MPA for 72 h. Proteoglycan synthesis was measured by incorporation of sodium [35S]sulfate into proteoglycans and proteoglycan degradation was measured by release of total and radiolabeled proteoglycan into the culture media. The size of the proteoglycans was assessed with size exclusion chromatography un...
Fernández-Varón E, Cárceles CM, Marín P, Martos N, Escudero E, Ayala I.To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. Methods: 6 healthy mature horses. Methods: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence ...
Nouws JF, Vree TB, Baakman M, Driessens F, Smulders A, Holtkamp J.The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/k...
Doherty TJ, Geiser DR, Rohrbach BW.The effect of i.v. acepromazine (0.05 mg/kg bwt), butorphanol (0.05 mg/kg bwt) and a combination of acepromazine and butorphanol on halothane minimum alveolar concentration (MAC) was determined in 7 mixed-breed ponies. Ventilation was controlled, and blood pressure and temperature were maintained within normal limits. Following the determination of baseline MAC, treatments were administered to each pony in a random manner. The control treatment was normal saline. The baseline halothane dMAC for the control group was 0.91 +/- 0.04%, and no significant change occurred after saline administration...
Gómez-Díez M, Muñoz A, Caballero JM, Riber C, Castejón F, Serrano-Rodríguez JM.Pharmacokinetic and pharmacodynamic of IV enalapril at 0.50 mg/kg, PO placebo and PO enalapril at three different doses (0.50, 1.00 and 2.00 mg/kg) were analyzed in 7 healthy horses. Serum concentrations of enalapril and enalaprilat were determined for pharmacokinetic analysis. Angiotensin-converting enzyme (ACE) activity, serum ureic nitrogen (SUN), creatinine and electrolytes were measured, and blood pressure was monitored for pharmacodynamic analysis. The elimination half-lives of enalapril and enalaprilat were 0.67 and 2.76 h respectively after IV enalapril. Enalapril concentrations ...
Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M.Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and,...
Storgaard IH, Kristensen J, Larsen C, Mertz N, Østergaard J, Larsen SW.Intra-articular depot injectables based on in situ suspension formation of ester prodrugs of nonsteroidal anti-inflammatory drugs are promising for management of joint pain. As candidates for this delivery approach, 5 diclofenac ester prodrugs comprising different imidazole-containing promoieties were synthesized and their physicochemical properties characterized. In vitro hydrolysis rates were investigated in buffer solutions, in 40% (v/v) human, equine, canine, and rat plasma, and in 80% (v/v) human and equine synovial fluid. Bioconversion of the prodrugs to diclofenac was found to be enzym...
Tokushige H, Kushiro A, Okano A, Maeda T, Ito H, Wakuno A, Nagata SI, Ohta M.Alfaxalone has a number of pharmacological properties which are desirable for constant rate infusion (CRI). Previously, the co-administration of alfaxalone and medetomidine is shown to be suitable for short-term anesthesia in horses. However, the use of alfaxalone-medetomidine CRI with inhalational anesthesia under surgical procedures have not been investigated in clinical cases. The aim of the present study was to evaluate the clinical efficacy of alfaxalone-medetomidine CRI in sevoflurane-anesthetized Thoroughbred racehorses undergoing arthroscopic surgery. Sevoflurane requirement, cardiovas...
Todhunter RJ, Fubini SL, Wootton JA, Lust G.The effect of different doses of methylprednisolone acetate (MPA) on proteoglycan and collagen metabolism of articular cartilage from normal equine joints was tested in vitro. Methods: Cultured explants were treated with 0, 0.0004, 0.004, 0.04, 0.4 and 4.0 mg/ml (approximately 10(-6)-10(-2) M) MPA for 72 h. Proteoglycan synthesis was measured by incorporation of sodium [35S]sulfate into proteoglycans and proteoglycan degradation was measured by release of total and radiolabeled proteoglycan into the culture media. The size of the proteoglycans was assessed with size exclusion chromatography un...
Letendre L, Kvaternick V, Tecle B, Fischer J.A rugged, sensitive and efficient liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative analysis of firocoxib in urine from 5 to 3000 ng/mL and in plasma from 1 to 3000 ng/mL. The method requires 200 microL of either plasma or urine and includes sample preparation in 96-well solid phase extraction (SPE) plates using a BIOMEK 2000 Laboratory Automated Workstation. Chromatographic separation of firocoxib from matrix interferences was achieved using isocratic reversed phase chromatography on a PHENOMENEX LUNA Phenyl-Hexyl column. The mobile phase w...
Menozzi A, Pozzoli C, Poli E, Colla C, Placenza G, Bertini S.We investigated the effects of different selective α -adrenergic receptor (AR) agonists (detomidine, medetomidine, xylazine, and brimonidine) on the contractions of horse-isolated bronchi induced by electrical field stimulation (EFS) and by carbachol. No effects were observed on the contraction induced by carbachol, while α -AR agonists reduced EFS-evoked contractions in a concentration-related fashion. The rank order of potency (pD ) was brimonidine (7.40 ± 0.20) >medetomidine (7.09 ± 0.24) >detomidine (6.13 ± 0.55) >xylazine (4.59 ± 0.16). The maximal effects (E ) were -56.3% ...
Hunt JM, Gerring EL.Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the pr...
Ensink JM, Moi A, Vulto AG, Tukker JJ.Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the...
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...
Lakritz J, Wilson WD, Marsh AE, Mihalyi JE.To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals. Methods: 6 healthy foals, 3 to 5 months old. Methods: Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of eryth...
Steel CM, Bolton JR, Preechagoon Y, Charles BG.The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by...
Hubbell JA, Muir WW.The rate of rise of arterial partial pressure of carbon dioxide (PaCO2) was determined in 49 apneic halothane-anesthetized horses following controlled ventilation. Drugs given for induction of anesthesia did not affect the rapid rate of rise of PaCO2 during the first minute after controlled ventilation, the PaCO2 at 1 minute after controlled ventilation, or the PaCO2 at which spontaneous ventilation began. Horses given xylazine-ketamine for induction of anesthesia had a significantly (P less than 0.05) faster rate of rise of PaCO2 after 1 minute following controlled ventilation than did horses...
Kitzman JV, Wilson RC, Booth NH, Hendricks HL, Bush PB.The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volu...
Mendoza FJ, Serrano-Rodriguez JM, Buzon-Cuevas A, Perez-Ecija A.Alternatives to surgical castration are necessary for controlling the sexual behaviour of stallions with breeding potential in training and competition. Flutamide is a potent selective non-steroidal androgen receptor competitive antagonist that has been used in human beings as an anti-androgenic drug. In this study, the pharmacokinetics and bioavailability of flutamide and its main active metabolite, 2-hydroflutamide, were determined in seven healthy mature stallions. Single doses of flutamide (1mg/kg intravenously, 1mg/kg orally in fasted horses, 5mg/kg orally in fasted horses and 5mg/kg oral...
Johansson IM, Kallings P, Hammarlund-Udenaes M.The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of ...
Young LE, Blissitt KJ, Clutton RE, Molony V.To evaluate the hemodynamic effects of a 60-minute infusion of dopexamine in horses anesthetized with halothane. Methods: 7 adult Thoroughbreds. Methods: Measurements of left ventricular function obtained by transesophageal Doppler echocardiography and cardiac catheterization. Results: Infusion of dopexamine (4 micrograms/kg of body weight/min) significantly increased heart rate, cardiac output, maximal rates of increase and decrease of left ventricular pressure, and maximal acceleration and maximal velocity of aortic blood flow. Left ventricular ejection time significantly increased, and pre-...
Pedersoli WM, Belmonte A, Purohit RC, Ravis WR.The pharmacokinetics of gentamicin were studied in six healthy mature horses of mixed breeding and of both sexes. A parenteral preparation of gentamicin sulfate (5% aqueous solution) was administered rapidly (IV) at the dosage level of 5 mg/kg of body weight. Venous blood samples were taken at 0 (base line), 0.083, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after gentamicin administration. Serum gentamicin was measured by a radioimmunoassay technique. The gentamicin concentration data was fitted to a one- and two-compartment open model with first-order elimination from ...
Afonso T, Giguère S, Rapoport G, Berghaus LJ, Barton MH, Coleman AE.Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy. Objective: The degree of serum ACE inhibition varies considerably between drugs. Methods: Eight healthy adult horses. Methods: Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05...
Knych HK, McKemie DS, Kanarr KL, White SD.To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses. Methods: 12 healthy adult horses. Methods: In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg...
Foster AP, Cunningham FM, Andrews MJ, Lees P.The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF-induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibit in vitro platelet aggregation in a dose-dependent, competitive reversible manner (pA2 = 7.21). Co-administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF-induced neutrophil accumulation in vivo in equine skin. Intravenous (i.v.) administration of both drugs at a dose o...
Haughan JE, Missanelli JR, You Y, Stefanovski D, Soma LR, Robinson MA.Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( ) and beta ( ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( ) was ...
Delbeke FT, Debackere M, Desmet N, Stevens M.Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailabi...
Smith CM, Steffey EP, Baggot JD, Dunlop CI, Farver TB.Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent vol...
Hart KA, Sherlock CE, Davern AJ, Lewis TH, Robertson TP.N-butylscopolammonium bromide (NBB) is an anticholinergic agent used to treat spasmodic colic in horses. Intestinal smooth muscle spasm also occurs in horses with intraluminal intestinal obstructions, such as ileal impactions. The antispasmodic effects of NBB may be useful in managing ileal impactions, but the effects of NBB on equine ileal smooth muscle are unknown. Objective: To investigate the effects of NBB on spontaneous and induced contraction of the equine ileum in an ex vivo model. Methods: Ex vivo biomechanical study assessing contractile properties in isolate equine ileal smooth musc...
Vickroy TW, Chang SK, Chou CC.The goals of this study were to elucidate the temporal and quantitative relationships between caffeine and its major bioactive metabolites in blood and cerebrospinal fluid (CSF) and to characterize the pharmacokinetic-pharmacodynamic relationship for caffeine-induced changes in spontaneous locomotor activity in the horse. We hypothesized that caffeine and its metabolites distribute efficiently into the CSF to antagonize adenosine A1 and A2a receptors and that spontaneous locomotor activity correlates well with caffeine and/or metabolite concentrations in CSF and blood. A microdialysis system w...
McGorum BC, Nicholas DR, Foster AP, Shaw DJ, Pirie RS.Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid ...
