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.
Chapman DI, Marcroft J.1. The metabolism of (±)-[14C]noradrenaline in horses has been studied. The plasma half-life of radioactivity following intravenous injection was 95 min.
2. Two horses each excreted about 80–85% of the radioactivity in the urine in 15 h after rapid intravenous injection and about 75% of the excreted radioactivity has been identified.
3. The unchanged drug in the urine accounted for less than 1% of the dose and 3-methoxynoradrenaline for about 7%. The main metabolites were 4-hydroxy-3-methoxymandelic acid (22%), 4-hydroxy-3-methoxybenzoic acid (13%) and 4-hydroxy-3-methoxyphenylglycol ...
Manohar M, Goetz TE, Sullivan E, Griffin R.The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days...
Garcia P, Paris AC, Leufroy A, Popot MA, Bonnaire Y.A quantitative method, using LC/ESI-MS(n) with a quadrupole linear ion trap mass analyzer, has been developed for the analysis of ipratropium cation in horse plasma and urine. The method applies solid-phase extraction with WCX cartridges for plasma and MM2 cartridges for urine, prior to analysis by LC/ESI-MS(n). The efficiency of extraction combined with the sensitivity and the selectivity of MS(n) allows for the quantification of ipratropium cation at picogram per milliliter levels. The analytical capabilities of the method have been successfully checked by the quantitative analysis of ipratr...
Hanson RR.Suitable use of prophylactic antimicrobial drugs for wounds depends on the accurate selection of appropriate antibiotics, dosing regimen, and duration of use. Regional intravenous delivery and intraosseous infusion of antibiotics are pivotal to a successful outcome for deep-rooted infections, inadequately perfused tissue, and infected wounds containing biofilm. Antibiotic-impregnated polymethylmethacrylate beads are predominantly helpful for wounds that have a poor blood supply and for those containing surgical implants that must remain in place.
Younkin JT, Santschi EM, Kukanich B, Lubbers BV, Warner M.Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24-hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2-hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentration...
Dirikolu L, Lehner AF, Hughes C, Karpiesiuk W, Camargo FC, Harkins JD, Woods WE, Bosken JM, Boyles J, Troppmann A, Fisher M, Tobin T.Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine th...
Cunningham FM, Andrews M, Landoni MF, Lees P.Calcium ionophore A23187 induced time and concentration dependent production of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5-lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore-induced LTB4 synthesis by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30 +/- 0.75 microM for BAY Y 1015 and BAY X 1005, r...
Werners A, Karasek I, Butler C, Yeatts J, Enomoto H, Baynes R.Several different tick species are known to infest horses. Aside from causing serious health and welfare issues, including anaemia, ill thrift, and immunosuppression, ticks can transmit a variety of important, sometimes zoonotic, pathogens. The successful prevention and treatment of tick infestations have been described, but the information is scarce and, in many instances, anecdotal. Here we describe a practical and affordable prevention of tick infestation by using abamectin-impregnated cattle ear tags affixed to a safety collar. We have assessed the radial distribution of abamectin by analy...
Hagedorn HW, Meiser H, Zankl H, Schulz R.The misuse of opiates in racehorses relates to their effect of increasing locomotor activity. Because methadone, a narcotic analgesic, has been suspected of use as a doping compound in the past, it was added to the list of banned drugs and should be considered in doping control. Because the literature fails to provide information on detection of methadone in blood or urine of horses, an enzyme-linked immunosorbent assay was developed to monitor this narcotic in equine body fluids. Combined with high-performance liquid chromatography, the immunoassay also served to confirm positives indicated b...
Prichard RK, Geary TG.Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace throughout the world in nematode parasites of small ruminants and is of increasing concern in horses, cattle, dogs and other animals. It is suspected in Onchocerca volvulus in humans. In most animals, resistance first arose to the avermectins, such as ivermectin (IVM), and subsequently to...
Söylemez Z, Ozer I.The inhibition of horse plasma cholinesterase by propranolol showed characteristics which depended upon the identity of the substrate used. With butyrylthiocholine as substrate, the inhibition showed a first-order dependence on inhibitor concentration, and was characterized by a Ki of 8 microM (pH 7.4, 20 degrees C). With p-nitrophenylbutyrate as substrate, a biphasic v-1 versus [I] relationship was obtained. The biphasic curve could be resolved into two components, with apparent Ki's of 9 microM and 1.3 mM. Use of butyrylthiocholine as alternative substrate resulted in partial inhibition of p...
Hayami A, Darwish WS, Ikenaka Y, Nakayama SM, Ishizuka M.There is little information about drug metabolism and pharmacokinetics in horses. Therefore, it is necessary to characterize the profiles of drug metabolites for the safe use of drugs. In this study, we focused on cytochrome P450 enzymes (CYPs), which represent an important enzyme group to determine pharmacological effects of drugs. We chose diazepam as the drug of choice for this study. The aim of this study was to elucidate the metabolic pathway of diazepam in horses in comparison with rats, and to clarify CYP subfamilies responsible for diazepam metabolism in horses. Our results showed tema...
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...
Lavy E, Ziv G, Glickman A.An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus asinus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45-60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2 beta) was 209 +/- 36 min, the apparent vol...
Ferrante PL, Freeman DE, Ramberg CF, Kronfeld DS.Multicompartmental analysis was applied to study the kinetics of D-xylose distribution after IV administration to healthy mares deprived of food for 12 and 96 hours. Urinary excretion of D-xylose was measured over a 15-hour period after administration. The plasma D-xylose concentrations in this study were in the range found after oral tolerance testing. The disposition of D-xylose was described by a two-compartment model with linear kinetic characteristics. Total volume of distribution decreased significantly (P < 0.025) from 0.270 L/kg of body weight after the 12-hour period of food depriv...
Sisodia CS, Kramer LL, Gupta VS, Lerner DJ, Taksas L.Pharmacological disposition of chloramphenicol was studied in horses. Minimum levels of the antibiotic (greater than or equal to 5 mu g/ml) in blood or plasma recommended to combat infections could not be achieved by 4.4 and 8.8 mg/kg I.V. or 30 and 50 mg/kg I.M. or 30 mg/kg oral (as palmitate salt) doses of chloramphenicol. Increasing the dose to 19.8 and 26.4 mg/kg I.V. provided such levels for about two and three hours respectively. A combination of 20 mg/kg I.V. and 30 mg/kg I.M. administered simultaneously did not provide more prolonged levels than 26.4 mg/kg I.V. alone. Chloramphenicol s...
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 ...
Landuyt J, Delbeke FT, Debackere M.The plasma concentrations of phenylbutazone (PBZ) and its major metabolites, oxyphenbutazone (OPBZ) and gamma-OH-phenylbutazone (OHPBZ) were determined for up to 72 h in six horses, following intravenous (i.v.) and intramuscular (i.m.) administration of 4 g phenylbutazone, 20 ml Phenylarthrite Ventoquinol (Vetoquinol Spécialités Pharmaceutiques Vétérinaires, Magny-Vernois, 70200 Lure, France). After i.v. dosing the plasma disposition was best described by a two-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 48 h, r...
Harðardóttir H, Murison PJ, Blissitt K, Olason S, Clutton RE.Ketamine at 2.2 mg/kg given i.v. is often used to induce anaesthesia for surgical procedures in horses under field conditions. Commonly, additional doses are needed to complete the surgery. We hypothesised that surgical conditions would be improved when 5 mg/kg of ketamine was used to induce anaesthesia, while induction and recovery qualities would not differ from those when 2.2 mg/kg ketamine was used. Objective: To compare the anaesthetic effects of two ketamine doses (5 and 2.2 mg/kg) during field anaesthesia for castration of horses. Methods: Prospective, randomised, blinded, clinical stud...
Dobler D, Gerber M, Schmidts TM, Runkel F, Schlupp P.Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model s...
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 ...
Luo Y, Rudy JA, Uboh CE, Soma LR, Guan F, Enright JM, Tsang DS.The method describes quantification and confirmation of flunixin in equine plasma by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS/MS). Samples were screened by enzyme-linked immunosorbent assay (ELISA) and only those samples presumptively declared positive were subjected to quantification and confirmation for the presence of flunixin by this method. The method is also readily adaptable to instrumental screening for the analyte. Flunixin was recovered from plasma by liquid-liquid extraction (LLE). The sample was diluted with 2 ml saturated phosphate buffer (pH ...
Chuang MS, Huang HH, Dixon KM, Chen KS, Mao CL, Chen CL.The pharmacokinetics of clenbuterol in equine urine and blood was investigated. Methods: Urine and blood samples were collected following 3-day multiple oral administrations. The samples were examined using enzyme-linked immunosorbent assay and further confirmed by solid phase extraction and capillary electrophoresis. Results: Urinary clenbuterol was detectable until day 14 after the last dose. The urinary excretion of clenbuterol was characterized by a biphasic pattern. The half-lives of the bi-exponential elimination (t(1/2alpha) and t(1/2beta)) for urinary clenbuterol were about 12.1 and 48...
Kim JY, Choi MH, Kim SJ, Chung BC.A high-performance liquid chromatographic-tandem mass spectrometric (HPLC/MS/MS) method for the determination of 19-nortestosterone and its esters (cyclopentanepropionate, phenylpropionate, and decanoate) in equine plasma is achieved using an atmospheric pressure chemical ionization (APCI) interface in selected reaction monitoring (SRM) mode. The two internal standards used were 16,16, 17-(2)H(3)-19-nortestosterone for 19-nortestosterone and methenolone acetate for its esters. The steroids studied were extracted from plasma samples with a mixture of diethyl ether/n-hexane (9:1, v/v). The quant...
Knych HK, Arthur RM, McKemie DS, Chapman N.Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug con...
Stanley S, Jeganathan A, Wood T, Henry P, Turner S, Woods WE, Green M, Tai HH, Watt D, Blake J.We have raised antibodies to morphine and etorphine and developed one-step enzyme-linked immunosorbent assays (ELISA) for these drugs as part of a panel of post race tests for drugs in racing horses. These tests are simple, can be completed in 2 h, and can be read by visual inspection. The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL. Cross-reactivity studies show that the antimorphine antibody cross-reacts well with levorphanol, hydromorphone, and oxycodone, while the anti-etorphine antibody showed no cross-reactivi...
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 ...
Houck EL, Papich MG, Delk KW.Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood ...
Ball MA, Rebhun WC, Trepanier L, Gaarder J, Schwark WS.The objectives of this study were to determine the concentration of itraconazole achieved in corneal tissue and aqueous humour after topical application of a 1% itraconazole ointment: to determine the effect of including dimethyl sulphoxide (DMSO) in the ointment on achievable ocular tissue itraconazole concentrations; and to assess if any gross or histopathologic ocular toxicity results from the topical application of 1% itraconazole with or without the addition of DMSO. The experimental trial consisted of 6 horses considered to have normal eyes. Each horse had one eye treated with 0.3 mL of ...
Keen JA, Hillier C, McGorum BC, Bunton D, Nally JE.Pharmacological evaluation of the unique equine laminar microvasculature is crucial to understanding its role in health and in diseases such as laminitis. However, separating the distinctive characteristics of arterial versus venous components of this complex vascular network has previously proved to be extremely difficult. Encased in a hard hoof capsule, isolation of individual blood vessels presents a considerable challenge. Exacerbating this difficulty, the laminar venous network is adapted to sustain high intravascular pressures and consequently has thickened walls, making the normally str...
Lyons ET, Drudge JH, Tolliver SC.The efficacy of 2 injectable formulations of ivermectin, administered intraorally at the dosage of 200 micrograms/kg of body weight, was evaluated against naturally occurring infections by abomasal nematodes in lambs in 2 controlled tests. One test (A) included 17 lambs treated with the equine formulation and 16 nontreated lambs. For the other test (B), 14 lambs were treated with the bovine formulation, and 12 were nontreated. In controlled test A, only mature nematodes were recovered, and removals were 98% to 100% for Haemonchus contortus, Ostertagia circumcincta male, O trifurcata male, Oste...
