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.
Sweeney CR, Soma LR, Beech J, Reef V, Simmons R.Serum and peritoneal fluid concentrations of ticarcillin were measured in 10 healthy adult horses from 0.5 to 8 hours after IV or IM administration of 44 mg/kg of body weight. After IV injection, the serum concentration at 30 minutes was 104.3 +/- 6.1 mg/L and the mean peak peritoneal fluid concentration (61.4 +/- 29.0 mg/L) occurred 2 hours after injection. The peak serum (28.3 +/- 5.5 mg/L) and the peak peritoneal fluid concentrations (19.2 +/- 6.0 mg/L) occurred 2 hours after the IM injection. Ticarcillin (greater than or equal to 2 mg/L) persisted in serum and peritoneal fluid for 6 hours ...
Sullins KE, Messer NT, Nelson L.Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against...
Ketelaars HC, Peters JG, Anzion RB, Van Ginneken CA.The isolation, partial identification and quantitative determination of four guaiphenesin glucuronides in plasma and urine of the horse is described. The identity of the glucuronides was checked by UV and fluorescence spectrophotometry, by NMR spectrometry and by mass spectrometry after permethylation. The applicability of the procedure to pharmacokinetic studies is demonstrated.
Engelking LR, Dodman NH, Hartman G, Valdez H.The acute 2-hour effects of isoflurane anesthesia on liver function and biliary excretion were examined in 2 ponies prepared surgically with chronic external biliary fistulas (T-tubes). Studies were conducted 2 to 8 months postoperatively with the enterohepatic circulation held intact between studies. Bile acid infusion IV (8.1 to 8.8 mumol/min) helped maintain bile flow and bile acid and bilirubin excretion during complete biliary diversion throughout each study. Following 3-hour control periods, anesthesia was induced and maintained at 1.3 to 1.5 minimal alveolar concentration plus O2 (spont...
Adams SB, Lamar CH, Masty J.Bipolar stainless steel electrodes were surgically implanted in 4 ponies to record myoelectrical and mechanical activity of the distal portion of the jejunum and pelvic flexure. After determining normal activity, the effects of neostigmine, xylazine, flunixin meglumine, dipyrone, panthenol, and atropine sulfate were determined. Flunixin meglumine, dipyrone, and panthenol had no effect on the motility of the jejunum or pelvic flexure. Xylazine and atropine sulfate decreased motility of the distal portion of the jejunum and pelvic flexure, with atropine sulfate having a greater effect and lastin...
Brown MP, Kelly RH, Gronwall RR, Stover SM.Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloram...
Schatzmann U, Girard P.The paper describes the problems of injection anaesthesia in the horse. Different commonly used methods, drugs and drug combinations are explained. Their actions and side-effects are compared and discussed.
Schatzmann U, Girard P.This paper summarizes causes of cardiovascular complications. Treatment of drug related hypotension as well as etiology and therapy of cardiac arrest are discussed.
Löscher W, Jaeschke G, Keller H.The pharmacokinetics of ascorbic acid were studied in 29 horses after intravenous (iv), subcutaneous, intramuscular (im) and oral administration. Following iv injection of 5 and 10 g ascorbic acid, respectively, a biphasic decline of ascorbic acid serum levels was found, indicating that the vitamin distributes in the body according to a two-compartment open model. The apparent volume of distribution (average value for Vd(ss) = 0.6 litre/kg) was approximately equivalent to the volume of total body water. The terminal half-life of the biexponential serum level-time curve (t1/2 beta) varied betwe...
Johansson IM, Schubert B.Flunixin is determined in equine plasma by liquid chromatography on LiChrosorb RP-18 with 70% methanol in phosphate buffer pH 3.1 as the eluent, with detection at 284 nm. Plasma is deproteinized with methanol and the supernatant is then injected directly into the system. With a short pre-column (5 x 3 mm i.d.), which is replaced after 25-40 injections of sample, 420 plasma samples could be analysed on one analytical column. The detection limit in plasma is 0.30 micromol/l (89 ng/ml) and the method can be used in pharmacokinetic studies.
Soma LR, Gallis DE, Davis WL, Cochran TA, Woodward CB.Phenylbutazone (PBZ) was administered (8.8 mg/kg of body weight) every 24 hours for 5 consecutive days, orally for the first 4 days and IV on day 5. The half-life (t 1/2) after this daily administration was 6.2 hours and the volume of distribution was 0.152 +/- 0.014 L/kg; the bioavailability after oral administration was 91.8 +/- 2.5%. The plasma concentration of PBZ at experimental hour (EH) 24 (24 hours after the 1st oral dose) was 1.7 +/- 0.39 micrograms/ml and increased to 4.2 +/- 0.29 micrograms/ml at EH 48 (24 hours after the 2nd oral dose). Values at EH 72, 96, and 120 (24 hours after ...
Schwark WS, Ducharme NG, Shin SJ, Beilman WT, Elwell JT.Serum levels of phenoxymethyl penicillin (penicillin V; Pen V) were measured following oral administration of two different formulations of the drug to five healthy horses. The mean serum concentration profile was described by a two-compartment model with a first order rate of absorption. Half-lives of the absorption, distribution and elimination phases were, respectively, 0.199 +/- 0.035, 0.362 +/- 0.060 and 3.650 +/- 0.575 hours. The distribution of the drug to body fluid compartments other than serum was examined. Mean peak levels of Pen V in serum, synovial fluid, peritoneal fluid and urin...
Nilsson K, Larsson PO.Horse liver alcohol dehydrogenase was immobilized on glycerylpropyl-silica (10 micron, 1000-A pores) activated with 2,2,2-trifluoroethanesulfonyl chloride (tresyl chloride). The coupling and activity yield was almost 100%. The coenzyme-binding sites were equivalent and virtually unaffected by the immobilization process, as judged from Scatchard plots and active-site titrations. The silica-bound enzyme, packed in steel columns, was integrated with HPLC equipment and then successfully used for chromatography of adenine nucleosides, adenine nucleotides, and triazine dyes. Dissociation constants w...
Ducharme NG, Dill SG, Shin SJ, Schwark WS, Ducharme GR, Beilman WW.This preliminary study evaluated phenoxymethyl penicillin (Penicillin V) as an alternative to parenteral administration of penicillin in horses. Penicillin V was administered orally to five horses at two different doses and plasma levels of the drug were determined at timed intervals. The results were evaluated by regression analysis. Following the administration of penicillin V at a dose of 66,000 IU/kg or 110,000 IU/kg, the mean peak plasma levels obtained were 1.55 micrograms/mL and 2.34 micrograms/mL respectively. A plasma level two to four times above the minimal inhibitory concentration ...
Brumbaugh GW, Martens RJ, Knight HD, Martin MT.Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49-57 kg (mean +/- 1 standard deviation = 53.19 +/- 2.66) each, and were 1-9 days (4.5 +/- 2.56) of age. The drug was rapidly distributed and followed first-order elimination. Mean pharmacokinetic values were: zero-time serum concentration (C0) = 36.14 microgram/ml (+/- 14.80); apparent specific volume of distribution (Vd) = 1.614 1/kg (+/- 0.669); and elimination rate constant (K) = 0.7295 h-1 (+/- 0.3066) which corresponds to a biological half-life (t1/2) = 0.95 h. These values d...
Wilson RC, Moore JN, Eakle N.The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given end...
Collins P.In vitro sensitivity data suggest that acyclovir should be effective against clinical manifestations of herpes simplex virus types 1 and 2, varicella-zoster virus and possibly Epstein-Barr virus. The clinical potential against herpes simplex virus types 1 and 2 is further supported by results in animal models. Human cytomegalovirus and the veterinary herpes viruses, with the possible exception of equine herpes virus type 1, may be insufficiently sensitive to be amenable to treatment.
Riviere JE, Coppoc GL, Hinsman EJ, Carlton WW, Traver DS.Gentamicin pharmacokinetics and nephrotoxic potential were evaluated in twelve 2 to 3 month-old horses. Whereas recent evidence in our clinic indicated that young horses may be especially susceptible to gentamicin nephrotoxicity, young rabbits and rats are usually resistant. Gentamicin (4.5 mg/kg) was given by rapid intravenous injection. Serum gentamicin concentrations over a 13-hour period were fitted to an open, two-compartment, pharmacokinetic model. Subsequently, the same horses were divided into groups of 3 horses each. Each group received 0, 2.2, 4.4 or 8.8 mg gentamicin/kg, intramuscul...
Brumbaugh GW, Thomas WP, Enos LR, Kaneko JJ.Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 microgram digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (+/- 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (+/- 0.45) at a mean of 2.29 h (+/- 1.52) after administration. A second rise in serum digoxin concentration started about 6-8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (+/- 5.96). At a dose of 22 microgram digoxin/kg body...
Science (New York, N.Y.)August 26, 1983
Volume 221, Issue 4613 823-828 doi: 10.1126/science.6308762
Campbell WC, Fisher MH, Stapley EO, Albers-Schönberg G, Jacob TA.Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet kn...
Dumasia MC, Houghton E, Bradley CV, Williams DH.The metabolism and urinary excretion of 1,2(n)-3H-1-dehydrotestosterone were studied in cross-bred gelded horses. Approximately 40% of the dose was excreted in 24 h. The steroid metabolites were extracted by Amberlite XAD-2 resin and fractionated into glucuronides and sulphoconjugates. Unchanged 1-dehydrotestosterone was the only component identified by gas chromatography mass spectrometry after solvolysis of the sulphoconjugates. Positive and negative ion fast atom bombardment mass spectra were obtained on the purified 1-dehydrotestosterone sulphoconjugate isolated from horse urine and on the...
Roberts MC, Seawright AA.Colic was induced in horses and ponies following topical or intravenous (iv) administration of amitraz, a formamidine acaricide. The condition was characterised by rapid cessation of intestinal sounds, stasis, extensive impaction and tympany throughout the large colon. Three animals that were necropsied had a faecalith obstructing the proximal small colon aboral to marked colonic impaction. A reproducible and reversible impaction colic syndrome could be induced by an iv injection of 1 mg amitraz/kg body weight in solvent. There were immediate central nervous system and intestinal signs. Large ...
Thijssen HH, van den Bogaard AE, Wetzel JM, Maes JH, Muller AP.The pharmacokinetics of racemic warfarin were studied in 6 adult horses. After IV administration, the plasma concentration of warfarin showed a biphasic decline in time. Analysis of the data, according to 2-compartment kinetics, revealed the following constants: biological half-life was 13.3 hours, apparent volume of distribution was 0.46 L X kg-1, body clearance was 25.3 ml X hour-1 X kg-1. Warfarin was bound (91.5%) to plasma proteins. Unchanged warfarin was not detected in the urine. Absorption from the gastrointestinal tract was almost complete. Concentrations of warfarin in tissue were ex...
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...
Chou CC, Webb AI, Brown MP, Gronwall RR, Vickroy TW.Concentrations of caffeine (CA) and two metabolites were measured simultaneously in venous blood and splenius muscle of adult horses using a semi-automated in vivo microdialysis sampling technique. Dialysates from muscle and jugular vein were collected continuously for 48 h and drug levels were determined by high performance liquid chromatography (HPLC). Following i.v. injection, CA (3 mg/kg) attained a peak blood level of nearly 5400 +/- 600 ng/mL and decreased with a half-life of 15.3 +/- 0.7 h. Pharmacokinetic and statistical comparisons between CA concentrations in jugular dialysates and p...
Sokół R, Raś-Noryńska M, Michalczyk M, Jasiecka A, Ziółkowski H, Jaroszewski J.The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug's pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment,...
Ferreira da Cruz FS, Natalini CC, Pellin de Molnar BF, Beatriz da Silva Serpa P, Tisotti T, Midon M, Desessards de La Côrte F.This study aimed to evaluate the effects and lameness degree in horses administered tramadol after the P-glycoprotein (P-gp) enteric inhibitor ivermectin. Six horses were randomly distributed into three groups, which received two different doses of tramadol by a nasogastric tube: 1 mg/kg (tramadol group 1(GT1)), 4 mg/kg (tramadol group 4 (GT4)), and tramadol 1 mg/kg combined with ivermectin 0.2 mg/kg PO (ivermectin tramadol group (GT1 + Ive)), with one-week washout interval. Heart rate (HR), respiratory rate (RR), intestinal motility, body temperature, and the degree of lameness were eval...
Beech J.The emphasis of this article is on the clinical application of drugs in therapy for treatment of disorders of the lower respiratory tract. Medications discussed include those used to enhance clearance of secretions and those employed to prevent and/or alleviate bronchoconstriction. Antimicrobial agents and respiratory stimulants are briefly mentioned.
Smyth GB, Duran S, Ravis W, Clark CR.Histamine type II (H2) antagonists inhibit gastric acid secretion and are useful in treating gastric and duodenal ulcer disease. To provide some information on the pharmacokinetics of the H2 antagonist cimetidine, adult horses were given 3.3 mg/kg cimetidine intravenously (iv) or 3.3 and 10 mg/kg orally. Plasma cimetidine concentrations after 3.3 mg/kg orally were too low to measure. Following 3.3 mg/kg iv, cimetidine displayed two-compartment characteristics with a t1/2 of 0.083 +/- 0.039 h and t1/2 of 2.23 +/- 0.64 h. The total body clearance was 0.443 +/- 0.160 litre/h/kg and the mean resid...
Leung GN, Tang FP, Wan TS, Wong CH, Lam KK, Stewart BD.This paper describes the application of gas chromatography-mass spectrometry (GC-MS) for in vitro and in vivo studies of 6-OXO in horses, with a special aim to identify the most appropriate target metabolite to be monitored for controlling the administration of 6-OXO in racehorses. In vitro studies of 6-OXO were performed using horse liver microsomes. The major biotransformation observed was reduction of one keto group at the C3 or C6 positions. Three in vitro metabolites, namely 6alpha-hydroxyandrost-4-ene-3,17-dione (M1), 3alpha-hydroxyandrost-4-ene-6,17-dione (M2a) and 3beta-hydroxyandrost-...
Matthews NS, Lindsay SL.Minimum alveolar concentration (MAC) for halothane was measured before and after administration of intravenous butorphanol (0.022 and 0.044 mg/kg in bodyweight in nine yearling Shetland ponies. Arterial blood pressure, heart rate, respiratory rate, expired CO2 and rectal temperature was also measured. Even though mean MAC values decreased 10 and 9 per cent after the low and high doses respectively, they were not statistically different from those measured prior to butorphanol. Halothane MAC values increased after butorphanol in two ponies, both animals increasing locomotor activity and demonst...
Schumacher J, DeGraves F, Cesar F, Duran S.A local anaesthetic agent capable of temporarily resolving lameness after being administered perineurally would be helpful because rapid return of lameness would allow for other analgesic techniques to be performed within a short period of time. Objective: To determine if a 3% solution of ketamine hydrochloride (HCl), administered around the palmar nerves at the level of the base of the proximal sesamoid bones, can improve naturally occurring lameness that can be improved or abolished with a basilar sesamoid nerve block performed using lidocaine HCl and to compare the change in gait produced u...
McKinney AR, Ridley DD, Suann CJ.The phase I and phase II metabolism of the anabolic steroid methandrostenolone was investigated following oral administration to a standardbred gelding. In the phase I study, metabolites were isolated from the urine by solid-phase extraction, deconjugated by acid catalysed methanolysis and converted to their O-methyloxime trimethylsilyl derivatives. GC-MS analysis indicated the major metabolic processes to be sequential reduction of the A-ring and hydroxylation at C6 and C16. In the phase II study, unconjugated, beta-glucuronidated and sulfated metabolites were fractionated and deconjugated us...
Hunyadi L, Papich MG, Pusterla N.The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal hal...
Sweeney RW, Beech J, Simmons RD, Soma LR.The pharmacokinetics of ticarcillin and clavulanic acid following administration by the intravenous (i.v.) and intramuscular (i.m.) routes were investigated in six normal adult horses. Following i.v. administration, the ticarcillin disposition data conformed to a two-compartment model with an elimination half-life of 1.0 h. The disposition of clavulanic acid was described by a one-compartment model with an elimination half-life of 0.40 h. Following i.m. administration, the half-lives of both drugs were prolonged (ticarcillin 1.8 h, clavulanic acid 1.2 h). The bioavailability of ticarcillin was...
Tobin T, Blake JW, Sturma L, Arnett S.Procaine added to whole equine blood or diluted plasma was hydrolyzed with half times of approximately 9 and 12 minutes, respectively, at 37 C. This hydrolytic activity was sensitive to heating and physostigmine, but did not affect procainamide. At pharmacologic concentrations of procaine, the rate of the hydrolytic reaction depended directly on the concentrations of plasma or procaine in the system and was less in whole blood than in plasma. These properties are consistent with hydrolysis being due to plasma esterases operating at less than saturating procaine concentrations. These esterases ...
Aramaki S, Suzuki E, Ishidaka O, Momose A, Umemura K.The pharmacokinetics of caffeine (CAF) and its metabolites, dimethylxanthines, were examined in horses administered 2.5 mg/kg of CAF intravenously (i.v.), intramusculary (i.m.), or orally (p.o.). The plasma samples were extracted by Extrelut and the concentrations of CAF and metabolites were determined by high performance liquid chromatography (HPLC) with a short column. The pharmacokinetics of CAF after bolus i.v. injection were described by the assumption of a two-compartment model, and those of CAF after i.m. or p.o. administration were done by the assumption of a one-compartment model. The...
Raidal SL, Edwards S.To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. Methods: Twelve adult Standardbred and Thoroughbred mares. Methods: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses ...
Shults T, Combie J, Dougherty J, Tobin T.An operant conditioning apparatus for studies in equine pharmacology was constructed. Horses interacted with this apparatus by breaking a light beam and were rewarded with 30 ml of oats. Horses readily learned to use this apparatus and were trained to respond on a variable-interval-60 schedule. With this schedule, there was no direct relationship between the rate of light beam breaking and the reward. Horses thus developed their own individual response rates (ie, light-beam breaking rates), and these rates remained stable at between 5 and 35 responses/min for each horse over a period of months...
Franci P, Bertamini A, Bertamini O, Pilla T, Busetto R.A new volatile anaesthetic agent delivery system was tested in 15 horses undergoing scheduled surgical procedures. The delivery system consisted of a laptop computer (with dedicated software), a computer-controlled syringe driver (loaded with liquid isoflurane) connected to the inspiratory arm of a large-animal circle breathing system and a respiratory gas monitor, providing isoflurane end-tidal concentrations (ET(measured)) every 20 s to the computer. Following induction and connection to the breathing system, mechanical ventilation was started. The bodyweight (BW), fresh gas flow, breathing ...
Mama KR.Many new or modified injectable anesthetic techniques are available for use in horses. This increased availability allows the clinician to select the technique most appropriate for the patient and clinical circumstance. The use of sedative and anesthetic drugs in managing a variety of anesthesia-related and unrelated aspects of patient care is also increasing. As we begin to use these techniques in the clinical management of our patients, it is important to remember that, while there are more options, no single anesthetic agent or combination of agents is devoid of undesirable effects. Knowled...
Courtot D, Roux L, Mouthon G, Jeanin E.Doping with tranquilizers has appeared recently in horse-back riding sports. In this paper we study the effects of acepromazine, one of the main tranquilizers used, on various physiological and biochemical aspects of muscular activity (cardiac and respiratory rhythms, seric rates of glucose, urea, protein, creatine phosphokinase, glutamate oxalacetate transaminase, alkaline phosphatase). A low dose (0.02 mg/kg) of acepromazine is injected; the evolution of the variables is studied before and after a standardized effort. After the effort and during recuperation, acepromazine administration caus...
Clark ES, Moore JN.Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity of the circular and longitudinal muscle layers of the cecal body were measured in 7 conscious healthy horses during IV infusion of physiologic saline solution for 60 minutes (control), during a 60-minute IV infusion of dopamine (at dosages of 1, 2.5, and 5 micrograms/kg/min), and for 60 minutes after IV infusion of dopamine. The mean values for lateral cecal arterial blood flow during IV infusion of dopamine at a dosage of either 1 or 2.5 micrograms/kg/min were not significantly different from the...
Delbeke FT, Vynckier L, Debackere M.A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ w...
The locomotor pattern alterations produced after the administration of a sublingual detomidine gel was measured by an accelerometric method in horses. Using a randomized two-way crossover design, all animals (n = 6) randomly received either detomidine gel or a placebo administered sublingually. A triaxial accelerometric device was used for gait assessment 15 minutes before (baseline) and every 10 minutes after each treatment for a period of 180 minutes. Eight different parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral, propulsion, mediolater...
Parraga ME, Kittleson MD, Drake CM.The aim of this study was to determine if quinidine administration increases steady state serum digoxin concentration in horses. Digoxin (0.01 mg/kg q. 12 h per os) was administered to 6 horses for 7 days. Steady state was confirmed by identifying statistically indistinguishable peak and trough serum digoxin concentrations on Days 4, 5, and 6. On Day 6, serum digoxin concentration was measured at baseline and 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h after digoxin administration. On Day 7, quinidine (20 g at baseline and 10 g at 2, 4 and 6 h) was administered per os and serum digoxin concentration was...
Hood DM, Brumbaugh GW, Wagner IP.To determine whether a unique dihydropyridine (BAYTG 1000) would be beneficial in preventing laminitis in horses. Methods: 16 clinically normal adult horses. Methods: 8 pairs of horses were used in a controlled double-blind study, using sex- and age-matched horses randomly assigned to treatment or control groups. Horses were subjected to carbohydrate overload to induce laminitis. Treated horses were administered BAY TG 1000 (30 mg/kg, PO, q 24 h) for 3 days. Hoof wall surface temperature (HWST) and lameness were recorded at 4-hour intervals. The HWST was adjusted on the basis of time of onset ...
Underwood C, Collins SN, Mills PC, Van Eps AW, Allavena RE, Medina Torres CE, Pollitt CC.Pharmaceutical agents with potential for laminitis prevention have been identified. Many of these, including the MMP inhibitor marimastat, are impractical for systemic administration. This study compared local delivery of marimastat by regional limb perfusion (RLP) to systemic intravenous bolus dosing (SIVB), and established whether RLP results in local lamellar drug delivery. Six adult horses received 0.23 mg/kg of marimastat by RLP followed by 0.23 mg/kg marimastat by SIVB, with a 24-h washout period. Lamellar ultrafiltration probes sampled lamellar interstitial fluid as lamellar ultrafiltra...
Pusterla N, Vaala W, Bain FT, Chappell DE, Craig B, Schneider C, Barnett DC, Gaughan E, Papich MG.Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (Protazil) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five ...
Ortillés Á, Sanmartí J, Ríos J, Armengou L, Peña MT, Leiva M.To evaluate the effect of topical cyclopentolate hydrochloride (CH) on quantitative pupillometric readings (PR), tear production (TP), and intraocular pressure (IOP) in healthy horses. Methods: Fourteen client-owned horses. Methods: In a two-phase design study, each animal received 1% CH ophthalmic solution in the left eye [treated] and 0.9% NaCl in the right eye [control] (0.2 mL each). In the first phase (n = 7), TP, IOP, and PR assessment was performed by Schirmer tear test I, rebound tonometry and static pupillometry, at 1, 8, 24, 48, 72, 96, 120, 148, 172, and 196-hours post-instillati...
Keller H, Hashem A.In a study in the horse, the disposition, the pharmacokinetic parameters and the absorption rates of 3 formulations of phenylbutazone (injection solution, powder and paste suspension) have been determined. After i.v. injection, the half-life time of phenylbutazone has been determined to be 6.6-6.7 h. After oral administration, the absorption of phenylbutazone was found to be faster after administration via stomach tube than after direct application into the mouth. The absorption rat constant of the paste suspension was found to be higher than that of the powder (1.797-2.304 h-1 vs. 0.656-1.197...
Doran G, Hughes K, Rendle D, Edwards S.Pergolide is used to treat pituitary pars intermedia dysfunction (equine Cushing's Disease), a neurodegenerative condition associated with loss of dopaminergic inhibition of the pituitary in horses. After oral administration, only low concentrations of the drug are achieved in plasma, making drug detection and quantification difficult. While direct analysis of plasma using sensitive MS/MS techniques is possible, dirty plasma samples and mobile phase buffers can cause instrumentation to become rapidly incapacitated. A method using LC with fluorescence detection was developed for pergolide analy...
Myrna KE, Herring IP.To assess the efficacy and kinetics of a continuous infusion modality for topical ophthalmic drug delivery via subpalpebral lavage in horses. Methods: Five ophthalmically normal horses Methods: A constant-rate continuous delivery pump was used to apply 0.01% fluorescein solution to the eyes of five ophthalmically normal horses via subpalpebral lavage. Fluorescein was applied at a rate of 0.14 mL/h for 72 h. Tear samples were collected from the ventral conjunctival fornix at regular intervals via capillary tube and tear fluorescein concentrations were determined via spectral assay. Laboratory s...
