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.
Lees P, Tavernor WD.1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anae...
Lees P, Tavernor WD.1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood PCO(2) levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and PO(2) values.2. The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater chang...
CLARKE EG.This research article explores the topic of doping racehorses, looking at the history of the practice, the reasons for it, various methods used, and the substances utilized. It also presents […]
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Toutain PL, Ohta M.Fosfomycin (FOM) is an approved veterinary medicinal product for large animals in Japan, but Clinical breakpoint (CBP) for antimicrobial susceptibility test (AST) is not defined for animals. This study aimed at conducting a pharmacokinetics/pharmacodynamics (PK/PD) analysis to determine the PK/PD cutoff for the CBP in horses. Drug concentrations following single intravenous administration (IV) of 20 mg/kg body weight (BW) FOM in nine horses were measured using liquid chromatography/mass spectrometry. The data were modelled using a nonlinear mixed-effects model, followed by Monte Carlo simulati...
Reed RA, Berghaus LJ, Reynolds RM, Holmes BT, Krikorian AM, Sakai DM, Ishikawa Y, Knych HK.Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Unassigned: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at m...
Emmerich IU.In 2023, no new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. Two established veterinary active pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was also approved for horses, dogs, and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (pergolidmesilate) in a novel pharmaceutical formulation and a lower content of the active ingredient, one ...
Wood JM, Baum HP, Bews JP, Wachsmuth ED, Heusser C, Hofbauer KG.In this study, the hypotensive efficacy of R-3-36-16, a monoclonal antibody against human kidney renin, was investigated during chronic administration to a primate. R-3-36-16 was given by continuous intraperitoneal infusion with osmotic minipumps to normotensive marmosets fed a low-sodium diet in doses of 30 or 300 micrograms/kg/day for 14 days. The lower dose had no effect on blood pressure (BP) or plasma renin activity (PRA). After two days of treatment, the higher dose reduced PRA by 57% and lowered BP by 13 +/- 7 mm Hg. Although the hypotensive response persisted after 14 days of treatment...
Ferran AA, Roques BB, Chapuis L, Kuroda T, Lacroix MZ, Toutain PL, Bousquet-Melou A, Lallemand EA.Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation. Unassigned: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the glute...
Kilcoyne I, Nieto J, Nottle BF, Flynn H, Knych HK.Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. Objective: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Methods: Randomised cross-over in vivo experiment. Methods: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout per...
Ebeling-Koning NE, Fowler JT, DelBianco JD, Surmaitis RM.Veterinary medication exposure may result in human toxicity, with approximately 6,000 exposures to veterinary-only medications reported to poison centers in 2022. There is a paucity of literature on the management of poisoned patients secondary to pharmaceuticals intended for equine use. Pergolide is a dopamine and serotonin receptor agonist and is currently approved to treat equine Cushing's disease. It was previously approved in the United States (US) to treat Parkinson's disease in humans; however, it was withdrawn from the market in 2007 due to its association with valvular heart disease....
McCarrel TM, Cole C, Maxwell LK, Roe HA, Morton AJ.To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. Methods: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossov...
Knych HK, Blea J, Scollay M, Kass PH, McKemie DS.Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to "calm a horse's nerves." In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at vari...
Knych HK, Steinmetz SJ, Traynham ML, McKemie DS, Kass PH.Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of sin...
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic anal...
Shroff K, Stefanovski D, Reef VB, Kraus MS, Solis CN.Information about congestive heart failure (CHF) treatment in the horse is limited. Torsemide, an oral loop diuretic, is increasingly used in humans, dogs, and cats with CHF. Torsemide is well absorbed and induces diuresis in healthy horses, and its use in a horse with CHF has been reported. This retrospective descriptive study aimed to describe the use of torsemide in equids with CHF. Methods: 12 equids (10 horses, 1 miniature donkey, and 1 mule). Methods: Horses presented to a referral practice with clinical signs of congestive heart failure. Diagnosis was confirmed with echocardiography. Tr...
Kodaira K, Kakizaki M, Nagata SI, Ode H, Okano A, Tamura N, Mizobe F, Matsuda Y, Kurimoto S, Aida H.To investigate the pharmacodynamics and pharmacokinetics of rocuronium administered by bolus injection to sevoflurane-anesthetized horses. Methods: Prospective, experimental, crossover study. Methods: Five healthy adult Thoroughbred horses (body mass 368-470 kg, three females and two males). Methods: Each horse was anesthetized twice with sevoflurane and assigned to be administered rocuronium bromide intravenously: 0.2 mg kg (R02) or 0.4 mg kg (R04). There was a minimum 2 week washout period between experiments. During anesthesia, the peroneal nerve was stimulated (train-of-four) and neuromusc...
Guzmán JFC, Gontijo AS, Melgaço ES, Faria SA, Baldi MLC, Sousa LN, Wenceslau RR, Fantini P, Xavier ABDS, Beier SL.Morphine has significant clinical and analgesic effects in horses, but its impact on the gastrointestinal tract requires further understanding. This study assessed the analgesic and gastrointestinal effects of morphine in horses undergoing elective orchiectomy in the quadrupedal position. Thirty uncastrated male horses were randomly assigned to three groups: orchiectomy without morphine and sedation protocol (OSM), orchiectomy with morphine and sedation protocol (OM), and administration of morphine alone in the absence of orchiectomy (M). The anesthetic protocol involved acepromazine (0.05 mg/...
Bacon EK, Donnelly CG, Finno CJ, Haase B, Velie BD.Multimodal analgesic administration is a promising strategy for mitigating side effects typically associated with analgesia; nevertheless, variation in analgesic effectiveness still poses a considerable safety concern for both horses and veterinarians. Pharmacogenomic studies have started delving into genetic influences on varying drug effectiveness and related side effects. However, current findings have narrow implications and are limited in their ability to individualize analgesic dosages in horses. Hydromorphone and detomidine were administered to a cohort of 48 horses at standardized time...
Gao T, Liu X, Qiu D, Li Y, Qiu Z, Qi J, Li S, Guo X, Zhang Y, Wang Z, Gao X, Ma Y, Ma T.Cefquinome is used to treat septicemia caused by () and respiratory infections caused by subsp. in foals. However, studies reporting the use of cefquinome to target as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against using a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). Th...
Bardhi A, Lanci A, Mannini A, Castagnetti C, Barbarossa A.Background: Although antibiotic resistance is a well-known issue in veterinary medicine, studies proposing real-time therapeutic monitoring (TDM) are lacking. The objective of the present study was to develop a simple and rapid protocol for the real-time therapeutic monitoring of antibiotics in horses and dogs. Methods: A reliable TDM protocol should encompass guidelines for the definition of plasma/serum collection time points, sample management by the clinical staff, transportation to the laboratory, and the availability of robust and swift analytical technologies. Ampicillin and sulbactam w...
Sayler B, Manship AJ, Davis J, Taylor J, Gilliam L.Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chl...
Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM.Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a "moving target" along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better ef...
Kuroda T, Minamijima Y, Niwa H, Mita H, Nomura M, Ohta M.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the dosage regimens of trimethoprim/sulfamethoxazole for methicillin-resistant Staphylococcus aureus (MRSA) infections after intravenous (IV) and per os (PO) administration in horses. Methods: Trimethoprim/sulfamethoxazole plasma concentrations were measured in six horses after a single IV administration of 15 mg/kg (2.5 mg/kg trimethoprim and 12.5 mg/kg sulfamethoxazole) and PO administration of 30 mg/kg (5.0 mg/kg trimethoprim and 25.0 mg/kg sulfamethoxazole). The data were modeled using a nonlinear mixed-effects mode...
Sullivan J, Blea J, McKemie DS, Kass PH, Knych HK.The pharmacokinetics and pharmacodynamics of betamethasone following intra-articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty-four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC-MS/MS and pharmacokinetic parameters determined using a Population PK three-compartment model. The duration of pharmacodynamic effects was assessed by...
Auvinen JRE, Kritchevsky JE, Reinhart JM, Gochenauer AE, Jannasch AS, Han-Hallett Y.Manipulation of forms of rectally administered metronidazole to improve bioavailability in horses has not been reported. Objective: Evaluate the pharmacokinetics of 3 rectal metronidazole preparations compared to nasogastric (NG) administration. Methods: Seven healthy horses. Methods: Phase 1A was a randomized, 3-way crossover, single-dose pharmacokinetic study, and Phases 1B and 2 were non-randomized, single-dose follow-up studies. Metronidazole (20 mg/kg) was administered NG and rectally in water (RW20), as a rectal gel (RG), and in dimethyl sulfoxide (DMSO). Metronidazole (80 mg/kg) was a...
Shimizu Y, Sugai-Bannai M, Tanabe H, Saito K, Ito H, Tokushige H, Kamiya K, Hirano-Kodaira M, Yamada M, Leung GN.Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration stud...
Hoh RL, Mama KR, Morales CJ, McKemie DS, Kass PH, Knych HK.To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses. Methods: Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study. Methods: Six (study 1) and eight (study 2) horses, aged 3-14 years. Methods: In study 1, horses were administere...
