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.
Aramaki S, Suzuki E, Ishidaka O, Momose A.The effects of exercise on the metabolism of caffeine (CA) were studied 3h after administration of the drug to race horses which then underwent exercise sets (1000-m gallop). Analysis was made of pharmacokinetics of CA, changes in its plasma concentrations, its metabolites, i.e., theophylline (TP), theobromine (TB) and paraxanthine (PX), and the molar concentration ratios of CA to these metabolites. After exercise, AUC and t1/2 tended to decrease, and the concentration of CA decreased, while the concentrations of TP and TB significantly increased. The TP/CA ratio and TB/CA ratio significantly ...
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...
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...
Beech J, Lindborg S.Horses with hyperkalaemic periodic paralysis were challenged with an oral dose of potassium chloride, and the prophylactic efficacy of phenytoin, acetazolamide and hydrochlorothiazide was evaluated, with at least three weeks separating the trials of each drug. After the administration of potassium chloride without prophylactic medication the horses' clinical signs ranged from generalised fine muscle fasciculations to gross tremors, and weakness with occassional prolapse of the nictitating membrane; plasma potassium concentration increased significantly (P < 0.01) from 4.0 +/- 0.2 to 6.0 +/-...
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...
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...
Taylor PM, Luna SP, Sear JW, Wheeler MJ.Pharmacokinetics and some pharmacological effects of anaesthesia induced by a combination of detomidine, ketamine and guaiphenesin were investigated in eight ponies. Cardiopulmonary function was studied and plasma met-enkephalin, dynorphin, beta-endorphin, arginine vasopressin, adrenocorticotrophin, cortisol, 11-deoxycortisol and catecholamine concentrations were measured. The combination produced slight cardiorespiratory depression, hyperglycaemia and a reduction in haematocrit. There were no changes in plasma opioids, pituitary peptides or catecholamines. Plasma cortisol concentration decrea...
Horspool LJ, McKellar QA.The present study was designed to determine and compare the plasma disposition and pharmacokinetics of penicillin G sodium following intravenous (i.v.) administration to horses, ponies and donkeys. The plasma disposition and pharmacokinetics of penicillin G was similar in horses, ponies and donkeys (elimination half-lives--39.0, 27.3 and 31.5 min, respectively) and a dosage interval of 6-8 h would be suitable to treat infections caused by susceptible bacteria. Although penicillin G was absorbed rapidly following nasogastric administration, the systemic availability was low (0.12-0.34%), theref...
Turner RM, McDonnell SM, Hawkins JF.Ejaculation was pharmacologically induced in a 13-year-old Quarter Horse stallion with a spiral fracture of the radius. The owners desired to have semen from the stallion frozen prior to euthanatizing the horse, but because of the debilitating injury, standard methods of semen collection could not be used. With the stallion standing quietly in a stall, a plastic collection bag was positioned over the stallion's penis, and clomipramine hydrochloride (2.2 mg/kg of body weight, IV) was administered. Fifty-five minutes later, xylazine hydrochloride (0.5 mg/kg, IV) was administered. The stallion ej...
Hobo S, Aida H, Yoshida K.The present study was carried out to assessing the sedative effect of medetomidine and determining its optimal dose in thoroughbred horses. Excessive ataxia after sedative treatment is dangerous for horses. Therefore three doses which may cause sufficient sedation with only mild ataxia were examined. Response to stimulation and the severity of ataxia suggested that 7.5 micrograms/kg BW, i.v., is optimal.
Toutain PL, Lassourd V, Costes G, Alvinerie M, Bret L, Lefebvre HP, Braun JP.The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.05...
van Duijkeren E, van Klingeren B, Vulto AG, Sloet van Oldruitenborgh-Oosterbaan MM, Breukink HJ, van Miert AS.The in vitro activity of 17 antimicrobial drugs against strains of Salmonella typhimurium (n = 52), Salmonella thompson (n = 2), Salmonella heidelberg (n = 3), Salmonella hadar (n = 2), Salmonella enteritidis (n = 1), Salmonella infantis (n = 1) and Salmonella derby (n = 1) was tested using the agar dilution method. The strains were isolated from horses admitted to the Large Animal Clinics of Utrecht University. The majority of strains were susceptible to gentamicin, amikacin, kanamycin, enrofloxacin, ciprofloxacin, flumequine, colistine, furazolidone and ceftiofur. However, all strains of Sal...
Pass MA, Mogg TD.Amitraz and its active metabolite BTS27271 were given intravenously to ponies and sheep at equimolar doses of 1 mg/kg and 0.68 mg/kg, respectively, and the plasma concentrations of amitraz and BTS27271 estimated at various times thereafter. Amitraz was hydrolysed to BTS27271 in both species. Amitraz was undetectable in sheep plasma after approximately 5 min but persisted in the plasma of ponies for at least 90 min. The persistence of unmetabolized amitraz in ponies may have implications for the toxicity of amitraz in that species. The primary and secondary disposition half-lives of amitraz in ...
Owens JG, Kamerling SG, Barker SA.The pharmacokinetic properties of a single intravenous dose of ketoprofen (2.2 mg/kg) in plasma and synovial fluid were compared in four healthy animals and four horses with experimentally induced acute synovitis. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint. Ketoprofen was administered at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two-compartment model in most horses. The plasma harmonic mean half-life in healthy horses (0.88 h) was longer than in horses with synovitis ...
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 [...
Godber LM, Walker RD, Stein GE, Hauptman JG, Derksen FJ.Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following i.v. administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin agai...
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...
McKellar QA, Horspool LJ.Penicillin G was extensively (84.7 per cent) and amikacin moderately (14.4 per cent) degraded when incubated for one hour in a chloride buffer at pH 1.9 designed to mimic the equine gastric pH. Ampicillin and oxytetracycline were stable at pH 1.9. Penicillin and ampicillin were moderately stable (more than 90 per cent) when incubated in equine caecal liquor for three hours but were degraded by about 65 per cent after 24 hours. More than 80 per cent of the initial concentrations of amikacin and oxytetracycline were recovered after 24 hours' incubation in equine caecal liquor. The concentrations...
Hagedorn HW, Zuck S, Schulz R.An enzyme linked immunosorbent assay (ELISA) was developed to detect the beta 2-agonist clenbuterol in equine blood and urine. The antiserum was raised in rabbits, employing clenbuterol-diazo-BSA as antigen. Clenbuterol-diazo-horseradish peroxidase served as enzyme conjugate. The concentration of clenbuterol to decrease tracer binding by 50% (IC50 value) was found to be 27.50 +/- 4.20 pg/well (1.37 ng/ml). The antibody cross-reacted with salbutamol (30%), terbutaline (14%) and cimaterol (1%). Horse serum was used directly to screen for clenbuterol, while urine was employed diluted. Positive sc...
Guillaume D, Rio N, Toutain PL.The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administrati...
Roberts CJ, Jackson LS.The development, validation, and application of an ELISA for dexamethasone in equine urine is described. The drug-protein conjugate was immobilised in microtitre plate wells and antiserum raised against the same drug-protein conjugate was allowed to compete with sample or standard drug and the immobilised drug-protein conjugate. The proportion of antiserum binding to the immobilised drug-protein conjugate was detected using a biotinylated protein G/extravidin-alkaline phosphatase complex in situ and measurement of the substrate product. The method was used to detect the presence of drug-derive...
Anderson BH, Firth EC, Whittem T.Plasma (P), synovial fluid (SF) and lymph (L) concentrations of gentamicin were studied in two trials. A lymph vessel in the hindlimb was cannulated. The day after surgery (trial A), P and L samples were collected for 12 h after intravenous injection of gentamicin sulphate at 2.2 mg/kg dose rate. Approximately 48 h after surgery (trial B), the fetlock joint of the cannulated hindlimb was catheterized and P, SF and L samples collected for 12 h after a similar intravenous injection. The kinetic parameters were similar to those in other reports and did not differ between trials (P < 0.05). The P,...
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 ...
Bergstrom TC, Kilcoyne I, Magdesian KG, Nieto JE.To determine whether IV regional limb perfusion (IVRLP) performed in the cephalic vein with a wide rubber tourniquet (WRT) applied proximal and distal to the carpus results in a higher peak concentration (Cmax) of amikacin in the radiocarpal joint (RCJ), compared with the Cmax for IVRLP using a single WRT proximal to the carpus. Methods: 7 healthy adult horses. Methods: Horses underwent IVRLP using standing sedation with 2 g of amikacin sulfate diluted to 60 mL by use of saline (0.9% NaCl) solution in the cephalic vein with 2 different tourniquet techniques; proximal WRT (P) and proximal and d...
Guan F, Robinson MA, Soma LR.Etanercept is a protein-based medication for the treatment of human patients with rheumatoid arthritis and other autoimmune-based diseases; its pharmacological action is to inhibit and antagonize tumour necrosis factor alpha. Etanercept was rumoured to be used in horse racing in North America. To detect such use, the aim of this study was to develop a liquid chromatography-mass spectrometry (LC-MS) method for confirmation of etanercept in equine plasma. Etanercept was extracted from plasma by anti-human IgG antibody linked to magnetic beads. The analyte was reduced and alkylated, and then dige...
Boeckh S, Buchanan C, Boeckh A, Wilkie S, Davis C, Buchanan T, Boothe D.Following approval of a concentrated injectable formulation of enrofloxacin for cattle (Baytril 100 Injectable, Bayer Corp. Agricultural Division, Shawnee Mission, KS), equine practitioners have started administering this preparation both parenterally and orally to horses, despite the lack of pharmacokinetic data in this species. Six healthy horses received enrofloxacin at 7.5 mg/kg both orally and intravenously, with the sequence being randomly assigned and at least 1 week of washout allowed between administrations. Blood samples were collected from each horse at various intervals after drug ...
Tendillo FJ, Mascías A, Santos M, López-Sanromán J, De Rossi R, San Román F, Gómez de Segura IA.To determine the minimum alveolar concentration (MAC) of desflurane (DES) in the horse. Methods: Prospective study. Methods: Six healthy adult horses (three males and three females) weighing 370 +/- 16 kg and aged 9 +/- 2 years old. Methods: Anesthesia was induced with DES vaporized in oxygen via a face mask connected to a large-animal, semiclosed anesthetic circle system. The horses were endotracheally intubated and positioned in right lateral recumbency. Inspired and end-tidal DES were monitored using a calibrated Ohmeda RGM 5250 multigas analyzer (Ohmeda-BOC, Spain). The MAC of desflurane t...
Levionnois OL, Mevissen M, Thormann W, Spadavecchia C.The objective of this study was to assess a pharmacokinetic algorithm to predict ketamine plasma concentration and drive a target-controlled infusion (TCI) in ponies. Firstly, the algorithm was used to simulate the course of ketamine enantiomers plasma concentrations after the administration of an intravenous bolus in six ponies based on individual pharmacokinetic parameters obtained from a previous experiment. Using the same pharmacokinetic parameters, a TCI of S-ketamine was then performed over 120 min to maintain a concentration of 1 microg/mL in plasma. The actual plasma concentrations of ...
Manohar M, Goetz TE, Rothenbaum P, Humphrey S.The present study was carried out to examine whether pentoxifylline administration to horses premedicated with frusemide would attenuate the exercise-induced pulmonary arterial, capillary and venous hypertension to a greater extent than frusemide alone, thereby affecting the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Using established techniques, we determined right heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at rest and during exercise performed at maximal heart rate at a workload of 14 m/s on 3.5% uphill grade in the control (no medication...
Casbeer HC, Knych HK.Tolazoline is an α2-adrenergic receptor antagonist, used in veterinary medicine to antagonize the central nervous system depressant and cardiovascular effects of α2 receptor agonists. The pharmacokinetics and pharmacodynamic effects of tolazoline when administered subsequent to detomidine in the horse were recently reported, although the reversal of the sedative and cardiovascular effects following detomidine may not be complete. The current study therefore investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses...
Sams RA, Detra RL, Muir WW.The pharmacokinetics and metabolism of doxapram in horses administered intravenous (iv) doses of 0.275, 0.55 and 1.1 mg doxapram/kg bodyweight (bwt) were investigated. Plasma doxapram concentrations decreased rapidly after drug administration and the disappearance of doxapram from plasma was best described by a polyexponential equation. Median values of total body clearance were 10.9, 10.6 and 10.9 ml/min/kg bwt for the three doses and were independent of dose. The steady-state volume of distribution was approximately 1,200 ml/kg bwt and the median biological half-life ranged from 121 to 178 m...
Orsini JA, Park MI, Spencer PA.Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 ...
Delbeke FT, Debackere M.A high performance liquid chromatographic method to measure plasma and urine fenoprofen levels in equine biofluids is described. Liquid-liquid extraction with diethylether was used to isolate the drug from plasma and urine. The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-10 micrograms/mL and 0-20 micrograms/mL respectively from plasma and urine. Detection limits were 0.05 microgram/mL (2 mL plasma) and 0.2 microgram/mL (0.5 mL urine). This procedure was applied to ascertain the pharmacokinetics of a 3 g dose of fenoprofen calcium in a...
Hamamoto-Hardman BD, Steffey EP, Seminoff K, McKemie DS, Kass P, Knych HK.Although morphine has demonstrated antinociceptive effects in horses, its administration has been associated with dose-dependent adverse effects. In humans and rats, part of the analgesic effect of morphine has been attributed to the active metabolite, morphine-6-glucuronide (M6G). Although morphine can cause several undesirable effects, M6G has a more favorable safety profile. The objective of this study was to characterize the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of M6G following intravenous administration to a small group of horses. In Part ...
Kong N, Yi R, Zhao S, Sandhu J, Lam G, Loganathan D, Morrissey B.A sensitive hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method was developed and validated for the simultaneous detection and quantification of etilefrine and oxilofrine in equine blood plasma and urine. The method is highly sensitive and specific with good precision and accuracy. In plasma the limit of detection and limit of quantification are 0.03 and 0.1 ng/mL, respectively, for both analytes. In urine the limit of detection and limit of quantification are 0.3 and 1 ng/mL, respectively, for both analytes. The suitability of the method for doping con...
Dirikolu L, Lehner AF, Harkins JD, Woods WE, Karpiesiuk W, Gates RS, Fisher M, Tobin T.Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations p...
Souillard A, Audran M, Bressolle F, Jaussaud P, Gareau R.The pharmacokinetics of recombinant human Epo (rHuEpo) were investigated after subcutaneous administration to horses. Four horses received a single 30IU kg-1 dose of rHuEpo. One horse received three repeated doses of 120 IU kg-1 at 48 h intervals. Plasma erythropoietin (Epo) was measured by radioimmunoassay. In both cases pharmacokinetic parameters were evaluated using a one-compartment open model and first-order input and output rates. The mean values (+/-SD) for elimination half-life, CL/F, and Vd/F after a single dose were 12.9 +/- 3.34 h, 11.8 +/- 4.96 L h-1, and 233 +/- 126 L, respectivel...
Reed RA, Knych HK, Barletta M, Sakai DM, Ruch MM, Smyth CA, Ryan CA.To compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration. Methods: Randomized, masked, crossover design. Methods: A total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg. Methods: Horses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for ...
Hussein H, Ishihara A, Menendez M, Bertone A.Plasma pharmacokinetic (PK) and bone resorption biomarker [carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1)] analyses were performed following single and multiple oral dose protocols of a Cathepsin K inhibitor (VEL-0230) in horses. Outcomes included plasma and urine drug and CTX-1 concentrations. In the dose range study, 2, 4, and 8 mg/kg body weight (b.w.) doses were administered in a Latin square design to three mares and evaluated for 1 week. Based on the PK characteristics of VEL-0230, 4 mg/kg b.w. was selected for the dose interval study in which 3.25 days (d) and 7 d...
Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Serrano Caballero JM, Muñoz A.The pharmacokinetics and pharmacodynamics (PK/PD) of the angiotensin-converting enzyme inhibitor (ACEI) ramiprilat after intravenous (IV) and oral (PO) administration of ramipril have not been evaluated in horses. This study was designed to establish PK profiles for ramipril and ramiprilat as well as to determine the effects of ramiprilat on serum angiotensin converting enzyme (ACE) and to select the most appropriate ramipril dose that suppresses ACE activity. Six healthy horses in a cross-over design received IV ramipril 0.050 mg/kg, PO at a dose of 0 (placebo), and 0.050, 0.10, 0.20, 0.40 ...
Carregaro AB, Mataqueiro MI, Soares OA, Queiroz-Neto A.The study of caffeine in racing horses has been of growing concern in veterinary sports medicine since the Association of Racing Commissioners International (ARCI) stated that it has no valid therapeutic use in racehorses. We examined the kinetic alterations in the urinary excretion and salivary secretion of caffeine in seven horses subjected to urinary acidification using ascorbic acid because this procedure can simulate the acidosis that follows anaerobic exercise. They participated in two treatment groups: the control group (SG) received 500 ml of saline and then 2.0 mg kg(-1) caffeine i.v....
Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S.The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys ( = 5), aged 6-12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume ...
McKibbin LS, Cheng RS.This study showed that subcutaneous injection of a solution of D-amino acids produced effective analgesia in horses. It is postulated that systemic D-phenylalanine and D-leucine may become one of the safe, effective and nonaddictive drugs for acute and chronic pain treatment. These D-amino acids cause analgesia by presumably preserving brain endorphins. They may bind reversibly to enkephalinases and prevent enzymatic degradation of enkephalins.
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...
McKinney AR, Suann CJ, Stenhouse AM.An investigation has been conducted into the metabolism and urinary excretion of orally administered piroxicam and tenoxicam in the horse. The major component detected in urine after the administration of piroxicam was 5'-hydroxypiroxicam, which was detectable up to 24 h post-administration. Unchanged piroxicam was present only as a minor component. In contrast, unchanged tenoxicam was the major component observed after the administration of tenoxicam, being detectable for 72 h post-administration, while 5'-hydroxytenoxicam was a minor component. Phase II beta-glucuronide conjugation in each c...
Naidoo V, Gehring R.An overview of reports of suspected adverse drug reactions received by the Veterinary Pharmacovigilance and Medicines Information Centre during the period March 2001 to February 2002 is given. A total of 77 reports were received. The majority of reports involved suspected adverse reactions that occurred in dogs and cats. Most products implicated in the reports were Stock Remedies. The products were predominantly administered either by veterinarians or trained paraveterinary professionals. Although the majority of reports were received from veterinary pharmaceutical companies, the proportion of...
Maes A, Baert K, Croubels S, De Clercq D, van Loon G, Deprez P, De Backer P.A rapid method for the quantification of amiodarone and desethylamiodarone in animal plasma using high-performance liquid chromatography combined with UV detection (HPLC-UV) is presented. The sample preparation includes a simple deproteinisation step with acetonitrile. In addition, a sensitive method for the quantification of amiodarone and desethylamiodarone in horse plasma and urine using high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is described. The sample preparation includes a solid-phase extraction (SPE) with a SCX c...
Anderson F.With the approach of the menopause and the cessation of ovarian estrogen production, a number of uncomfortable and/or dangerous conditions may be manifested, and are all indications for estrogen replacement therapy. Various routes of estrogen administration are available--oral, subcutaneous implant, intravaginal, and transdermal--each having advantages and disadvantages. There is also a choice possible among replacement hormones, which include the natural estrogens, such as estradiol and estropipate; synthetic estrogens, for example, ethinyl estradiol and diethylstilbestrol; and conjugated equ...
Boyd EH, Allen WE.Plasma drug concentrations were measured after two commercially available potentiated sulphonamides, trimethoprim and sulfadoxine and trimethoprim and sulphadiazine, were infused daily for 2 and 3 days, respectively, into the uteri of pony mares which had been mated before ovulation. Intravenous administration of trimethoprim and sulfadoxine allowed uterine absorption of trimethoprim (23-43%) and sulfadoxine (29-34%) to be calculated. After intra-uterine administration trimethoprim and sulphadiazine were detected in the milk of a lactating mare. In order to maintain plasma concentrations likel...
Ellerbrock RE, Curcio BR, Zhong L, Honoroto J, Wilkins P, Lima FS, Giguere S, Canisso IF.Enrofloxacin may be an alternative antimicrobial for unresponsive cases of severe bacterial infections in pregnant mares. As pregnancy may affect drug bioavailability, distribution, metabolism and excretion, dose adjustment might be necessary. Objective: To determine the disposition of orally and intravenously administered enrofloxacin in pregnant and non-pregnant mares. Methods: Randomised cross-over experiment. Methods: Six light-breed, healthy pregnant mares (260 days gestation) were given a single dose of either intravenous (5 mg/kg bwt) or oral compounded (7.5 mg/kg bwt) enrofloxacin, ...
Cagnardi P, Ferraresi C, Zonca A, Pecile A, Ravasio G, Zani DD, Villa R.Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. It is not approved for use in horses, but could represent a valid tool for pain treatment in this species. Objective: The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses. The evaluation of the degree of cardiovascular stability, the intraoperative effect and postoperative analgesia obtained...
Debord J, Verneuil B, Bollinger JC, Merle L, Dantoine T.The enzymatic hydrolysis of butyrylcholine, catalyzed by horse serum butyrylcholinesterase (EC 3.1.1.8), was studied at 37 degrees C in Tris buffer (pH 7.5) by flow microcalorimetry. A convolution procedure, using the Gamma distribution to represent the impulse response of the calorimeter, was developed to analyze the microcalorimetric curves. After correction for buffer protonation, the hydrolysis reaction was found to be slightly endothermic, with Delta H=+9.8 kJ mol(-1). Enzyme kinetics was studied with both the differential and integrated forms of the Michaelis equation with equivalent res...
