The dose-response relationship in horses refers to the correlation between the dose of a substance, such as a drug or nutrient, and the magnitude of the response it elicits. This relationship is fundamental in pharmacology and toxicology, as it helps determine the appropriate dosage that achieves the desired therapeutic effect without causing adverse reactions. In equine studies, dose-response assessments are used to evaluate the efficacy and safety of medications, supplements, and other interventions. These studies involve varying the dose and observing the physiological or behavioral responses in horses, which may include changes in heart rate, blood parameters, or performance metrics. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, findings, and implications of dose-response relationships in equine medicine and nutrition.
Kamerling SG, Cravens WM, Bagwell CA.1. Detomidine is a novel veterinary sedative analgesic which is thought to act by stimulation of alpha 2 adrenoreceptors. The present study was undertaken to determine the direction, time course, and dose-response relationship of detomidine on specific autonomic responses in the unanaesthetized horse. 2. Detomidine was administered intravenously to eight adult thoroughbred racehorses at doses of 0.010-0.040 mg kg-1, according to a double-blind Latin square crossover design. Cardiac and respiratory rates, pupil diameter and rectal temperature were monitored for 180 min postinjection. 3. Detomid...
Dodman NH, Shuster L, Court MH, Patel J.Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.
Kamerling SG, Dequick DJ, Weckman TJ, Tobin T.Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fenta...
Costa G, Labadia A, Garcia-Sacristan A.The effects of verapamil, a calcium antagonist agent, were studied on smooth muscle preparations of the lower urinary tract of horses. Verapamil (2 X 10(-4) to 2 X 10(-8) M) relaxed the ureter, urethra and urinary bladder preparations contracted by potassium (127 mM), L-noradrenaline (2 X 10(-5) M), histamine (2 X 10(-5) M) and acetylcholine (2 X 10(-5) M). These results allow the conclusion that verapamil has a dose-dependent relaxing effect on smooth muscle of the lower urinary tract.
Kamerling SG, DeQuick DJ, Weckman TJ, Tobin T.The dose-related effects of intravenously administered fentanyl (0.010, 0.005, 0.0025 mg/kg) and saline were studied in mature performance horses using a rigorous experimental protocol. Fentanyl produced a dose-related prolongation of the skin twitch reflex latency but did not increase the hoof withdrawal reflex latency. Dose related increases in stepping frequency, cardiac and respiratory rats were observed following fentanyl, while changes in rectal temperature and pupil area were not. These data indicate that fentanyl, a prototypic mu-agonist, produces a syndrome characterized by analgesia,...
Muir WW, Sams RA, Ashcraft S.The hemodynamic, respiratory, and behavioral effects, as well as the pharmacokinetic properties of methocarbamol, were determined in horses. Heart rate, cardiac output, arterial and venous blood pressures, respiratory rate, and arterial blood gases did not change after IV methocarbamol (4.4, 8.8, 17.6 mg/kg) administration. There were no signs of behavior modification or ataxia observed. Analysis of plasma concentration time data indicated that the disposition of methocarbamol may be dose-dependent. Clearance and steady-state volume of distribution decreased as the dose increased. Plasma conce...
Thurmon JC, Steffey EP, Zinkl JG, Woliner M, Howland D.Xylazine given IV at doses of 0.5, 1.0, and 1.5 mg/kg to mares caused a significant (P less than 0.05) dose-related increase in serum glucose concentration and urine volume. Serum glucose concentrations as much as 150 mg/dl were recorded in mares after they were given the largest xylazine dose. The greatest urine volume, similar to changes in peak glucose concentration, always occurred during the first hour after dosing with xylazine and averaged 1.82, 3.93, and 5.68 ml/kg/hour after the 0.5-, 1.0-, and 1.5-mg/kg doses, respectively, were given. Urine osmolality and specific gravity were signi...
Klein L, Hopkins J.4-Aminopyridine was administered in incremental IV doses to healthy horses to evaluate cardiorespiratory and behavioral effects. Doses of 100 micrograms/kg produced apparent sensory discomfort, manifested by wiggling or curling of the lips and tongue, arching or stretching the neck, snorting, squealing, and coughing. At cumulative dosages of 300 to 500 micrograms/kg, muscle tremors, a stilted gait, and signs of excitement occurred. Once signs of excitement occurred, additional administration of 4-aminopyridine resulted in prolonged excitement consisting of severe muscle tremors and exaggerated...
Love DN, Rose RJ, Martin IC, Bailey M.Amoxycillin trihydrate was administered orally to 6 foals at dose rates of 13 mg/kg (low), 20 mg/kg (medium) and 30 mg/kg (high) and serum concentrations determined at intervals up to 8 h. Therapeutic serum levels of 1 microgram/ml persisted for 268 mins at a dose rate of 13 mg/kg, for 339 mins at 20 mg/kg and for 381 mins at 30 mg/kg. A 2 micrograms/ml serum level persisted for 198 mins at a dose rate of 13 mg/kg, for 268 mins at 20 mg/kg and for 311 mins at 30 mg/kg. To determine the spectra of its antibacterial activity, the minimum inhibitory concentrations of amoxycillin against 8 genera ...
Muir WW, Sams RA, Huffman R.The acute behavioral cardiopulmonary and pharmacokinetic effects of propoxyphene hydrochloride were studied in seven adult horses. Each horse was given three different dosages of propoxyphene (0.5, 1.0, 2.2 mg/kg) IV. Fourteen days was allotted between each drug administration. The lower IV dosages of propoxyphene (0.5, 1.0 mg/kg) resulted in no changes in indices of cardiopulmonary function. Four horses demonstrated a transient period of muscle fasciculations when given 0.5 mg of propoxyphene/kg. Horses given 1.0 mg/kg demonstrated a brief period of euphoria, ataxia, and muscle fasciculations...
Lyons ET, Drudge JH, Tolliver SC.Critical tests were conducted in 11 naturally infected horses to evaluate the anthelmintic activity of parbendazole. Single doses at the rates of 30, 20, 10, 5, or 2.5 mg/kg of body weight were administered by stomach tube to 1, 4, 2, 2, and 2 horses, respectively. Parbendazole was active against Parascaris equorum, Oxyuris equi, Strongylus vulgaris, Strongylus edentatus, and small strongyles throughout the range of doses. Generally, small numbers of P equorum were present, but apparently a dose rate higher than 2.5 mg/kg is necessary for complete clearance. Removal of O equi was virtually 100...
Mattison DR, White NB, Nightingale MR.The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) reduced the fertility of DBA/2N mice in a dose-dependent fashion. Control mice produced offspring at a rate of 0.91 pups/mouse per week. Treatment with BP at doses of 10, 100, 200, and 500 mg/kg decreased offspring production rates to 0.61, 0.20, zero and zero pups/mouse per week, respectively. BP also destroyed primordial oocytes in similarly treated mice. Treatment with BP at doses of 10, 50, 100, and 500 mg/kg destroyed 20%, 58%, 88%, and 100%, respectively, of the primordial oocytes in DBA/2N mouse ovaries. Dose-response curves ...
Verberne LR, Mirck MH.The toxicity of parbendazole in different doses was investigated with 52 horses and 16 ponies, in twelve groups. Side effects observed with the anthelmintic were laxation (soft dung, diarrhoea), anorexia, and listlessness. The seriousness of these symptoms depended greatly on the dose used. Half the therapeutic dose of parbendazole (2.5 to 3.75 mg/kg) administered on two consecutive days led, as a rule, to only slight toxic symptoms and proved highly effective with regard to gastro-intestinal nematodes occurring in horses and ponies. The utilisation of "standard powders" (not commercially avai...
Oxender WD, Noden PA, Bolenbaugh DL, Hafs HD.To determine the minimal effective dose of prostagiandin (PGF2alpha; tromethamine salt) given subcutaneously (SC), mares of mixed breeding (400 kg av body weight) were given 2-, 3-, 5-, and 10-mg doses from 7 to 9 days after ovulation. In some but not all mares given doses of 2 and 3 mg of PGF2alpha, luteolysis occurred, but doses of 5 or 10 mg of PGF2alpha were luteolytic in all mares. The 10-mg dose of PGF2alpha did not cause luteolysis in mares 1 day after ovulation, and caused luteolysis in only 2 of 5 mares on day 3 after ovulation. The same dose of PGF2alpha, however, caused luteolysis i...
Williams MR.Rats were injected intradermally with rabbit anti-ovalbumin serum and 3 hours later were challenged intravenously with ovalbumin and Evans Blue dye. Inflammatory lesions were produced within 20 minutes and their size was markedly dose-dependent. Attempts were made to interfere with this passive cutaneous anaphylaxis (PCA) by admixture of normal IgG with the rabbit anti-ovalbumin to measure the relative tissue binding affinities of IgG from various species. It was found that normal IgG from any of the species tested had an enhancing effect on PCA in rats. These immunoglobulins serially arranged...
Stellmann C, Petermann HG.After vaccination of chickens, rabbits, foals and horses, HI and SN antibody dose response curves were compared for A/Equi 1/Prague and A/Equi 2/Paris strains.
The two curves are parallel for a given strain and the relationship of HI and SN titres is constant, whatever the animal species.
The distribution of HI and SN titres varies for the two strains.
This variation, which is independent of animal species, may be related to the number of sites necessary for the antigenic-antibody response in vitro.
It is suggested that the testing of equine influenza vaccine be carried out in the ...
Stellmann C, Petermann HG.After vaccination of chickens, rabbits, foals and horses, HI and SN antibody dose response curves were compared for A/Equi 1/Prague and A/Equi 2/Paris strains.
The two curves are parallel for a given strain and the relationship of HI and SN titres is constant, whatever the animal species.
The distribution of HI and SN titres varies for the two strains.
This variation, which is independent of animal species, may be related to the number of sites necessary for the antigenic-antibody response in vitro.
It is suggested that the testing of equine influenza vaccine be carried out in the ...
Ensink JM, Barneveld A, Klein WR, van Miert AS, Vulto AG.The plasma disposition of ampicillin after intravenous administration at a dose rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral bioavailability of pivampicillin was determined in the same foals at four ages, ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours after administration. After intravenous administration, the mean distribution and elimination half-lives of ampicillin were 0.121 and...
Brosnan RJ, Steffey EP.We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses. Methods: Prospective randomized, blinded, experimental trial. Methods: Twelve healthy horses aged 12 +/- 6 years (mean +/- SD), weighing 565 +/- 20 kg, and with an equal distribution of mares and geldings. Methods: Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg(-1)). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior s...
Oxender WD, Noden PA, Bolenbaugh DL, Hafs HD.To determine the minimal effective dose of prostagiandin (PGF2alpha; tromethamine salt) given subcutaneously (SC), mares of mixed breeding (400 kg av body weight) were given 2-, 3-, 5-, and 10-mg doses from 7 to 9 days after ovulation. In some but not all mares given doses of 2 and 3 mg of PGF2alpha, luteolysis occurred, but doses of 5 or 10 mg of PGF2alpha were luteolytic in all mares. The 10-mg dose of PGF2alpha did not cause luteolysis in mares 1 day after ovulation, and caused luteolysis in only 2 of 5 mares on day 3 after ovulation. The same dose of PGF2alpha, however, caused luteolysis i...
Muir WW, Sams RA, Ashcraft S.The hemodynamic, respiratory, and behavioral effects, as well as the pharmacokinetic properties of methocarbamol, were determined in horses. Heart rate, cardiac output, arterial and venous blood pressures, respiratory rate, and arterial blood gases did not change after IV methocarbamol (4.4, 8.8, 17.6 mg/kg) administration. There were no signs of behavior modification or ataxia observed. Analysis of plasma concentration time data indicated that the disposition of methocarbamol may be dose-dependent. Clearance and steady-state volume of distribution decreased as the dose increased. Plasma conce...
Kamerling SG, Cravens WM, Bagwell CA.1. Detomidine is a novel veterinary sedative analgesic which is thought to act by stimulation of alpha 2 adrenoreceptors. The present study was undertaken to determine the direction, time course, and dose-response relationship of detomidine on specific autonomic responses in the unanaesthetized horse. 2. Detomidine was administered intravenously to eight adult thoroughbred racehorses at doses of 0.010-0.040 mg kg-1, according to a double-blind Latin square crossover design. Cardiac and respiratory rates, pupil diameter and rectal temperature were monitored for 180 min postinjection. 3. Detomid...
Pezzanite L, Chow L, Soontararak S, Phillips J, Goodrich L, Dow S.Equine veterinarians frequently inject aminoglycoside antibiotics intra-articularly, either to treat septic arthritis or for prophylaxis with other medications when injecting joints for osteoarthritis. Although aminoglycosides have been demonstrated to be toxic to equine mesenchymal stem cells (MSC), their effects on resident joint cells have not been previously investigated. Moreover, safe and effective intra-articular doses have not been defined. Objective: To determine effects of concentration, duration of exposure, pH and the presence of synovial fluid on the cytotoxic effects of amikacin ...
Williams MR.Rats were injected intradermally with rabbit anti-ovalbumin serum and 3 hours later were challenged intravenously with ovalbumin and Evans Blue dye. Inflammatory lesions were produced within 20 minutes and their size was markedly dose-dependent. Attempts were made to interfere with this passive cutaneous anaphylaxis (PCA) by admixture of normal IgG with the rabbit anti-ovalbumin to measure the relative tissue binding affinities of IgG from various species. It was found that normal IgG from any of the species tested had an enhancing effect on PCA in rats. These immunoglobulins serially arranged...
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...
Pearson G, Goodale M, Wakshlag J, Fortier L.The objective of this study was to determine the effects of an oral, commercially available, marine based omega-3 fatty acid (n3-FA) supplement on fatty acid characteristics in horse whole blood. Fifty healthy, adult horses of various light breeds were assigned to one of two treatment groups: Group 1 receiving 7.5g/day of the test supplement, and Group 2 receiving 15g/day of the test supplement. The supplement contained 0.092g docosahexaenoic acid (DHA) and 0.148g eicosapentaenoic acid (EPA) per gram. Therefore, Group 1 received 1.11g of EPA and 0.69g of DHA daily, while Group 2 received 2.22g...
Castro-Cuellar G, Cremer J, Liu CC, Queiroz-Williams P, Hampton C, Leise BS.To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Methods: Primary cultured equine articular chondrocytes from 3 healthy adult horses. Methods: Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-sol...
Foreman JH, Bergstrom BE, Golden KS, Roark JJ, Coren DS, Foreman CR, Schumacher SA.There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). Objective: The objective of this experiment was to compare the efficacy of various dosages of FM with a negative control. The hypothesis was that higher doses would result in improved efficacy in a dose-dependent manner when tested in a reversible model of foot lameness. Methods: Ten horses shod with adjustable heart bar shoes had weekly modified AAEP grade 4.0/5.0 lameness induced by tightening a set screw against the heart bar. Heart rate (HR) and lameness score...
Benbarek H, Ayad A, Deby-Dupont G, Boukraa L, Serteyn D.The purpose of this study was to explore the potential modulation of equine neutrophil oxidative burst by a series of classical NSAIDs which was subsequently monitored by the luminol or lucigenin-enhanced chemiluminescence (CL) technique. A significant dose-dependent inhibition of the luminol CL was observed with the majority of investigated drugs. This inhibition was very significant for phenylbutazone and Indomethacin; while for aspirin, a higher concentration is required. The action of Ketoprofen was significant during the first 5 min and only when the concentration was above 1 mM. Indometh...
Marquardt J, Heymer J, Heinz H, Adolf GR, Deegen E.Recombinant equine interferon-beta 1 (reqIFN-beta 1) induces an antiviral state in blood mononuclear cells (BMC) of horses. Maximal protection against replication of vesicular stomatitis virus is achieved 6 hours after treatment with IFN in vitro and in vivo. Duration of the protective effect depends on the dose of IFN in vitro and in vivo. Availability of reqIFN-beta 1 in cultures of BMC for up to 48 hours does not prolong the antiviral state. The protective effect on BMC after treatment with IFN has similar duration in vivo and in vitro. Monitoring of the effect of IFN in vivo is, thus, simp...
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...
Yu R, Jusko WJ.This study assesses the pharmacokinetics (PK) of published methylprednisolone (MPL) data in horses following intra-articular (IA) administration of MPL acetate (MPA) and the associated adrenal suppression. The concentrations of MPL/MPA in synovial fluid, blood, and urine, as well as hydrocortisone (HC) in plasma, were digitized from multiple sources in the literature. A minimal physiologically based pharmacokinetic model and a linked indirect response model with a circadian rhythm baseline were applied. Concentrations of MPA in joints followed a triexponential decay, converting to MPL. The cle...
