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.
Marzok M, Almubarak AI, Kandeel M, El-Khodery S.Epidural analgesia using the alpha-2 agonist detomidine (DE), alone or in combination with lidocaine (LD), is frequently employed for standing surgical procedures in horses, but its use has not been evaluated in donkeys. Methods: In a randomised controlled prospective trial, 24 healthy adult donkeys were assigned to four groups (n = 6), each receiving 40 μg/kg of DE, 0.22 mg/kg of LD, combined DE and LD (DELD) or 0.9% sterile normal saline epidurally. After epidural injection of each treatment, the onset, degree and duration of sedation and anatomical extension of anti-nociception were obse...
Maney JK, Dzikiti BT, Escobar A, Knych HK, Bennett RC.Morphine is the prototypical μ-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. Objective: To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. Methods: In vivo experiment. Methods: Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1 mg/kg bwt (LDM), or morphine 0.5 mg/kg bwt (HDM) in a randomised order with a minimum 1-week washout period. Mechanical nociceptive thresholds (...
Sanches GL, Ribeiro LMF, Motta AP, Petrucci LBDV, Gobbi FP, Quirino CR, Di Filippo PA.This study aimed to compare the antinociceptive effects of tramadol 5% and lidocaine 2% on mental nerve block in horses of the Brazilian Pony breed. Eight adult non-pregnant mares were used in this study. The ponies were tranquilized with acepromazine (5 µg kg, IV), and the infiltration of the mental foramen was performed in Treatment 1- tramadol 5% (T, 150 mg) or Treatment 2- lidocaine 2% (L, 60 mg), both at a total dose of 3 ml in each foramen. Heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal te...
Peraza J, Hector RC, Lee S, Terhaar HM, Knych HK, Wotman KL.Acetaminophen (paracetamol) is increasingly used to treat painful conditions in horses but its ocular penetration has not been studied. Objective: To determine whether orally administered acetaminophen penetrates the aqueous humour of the normal equine eye and report an aqueous humour:serum acetaminophen concentration ratio in horses. Methods: In vivo experiment. Methods: Six privately owned horses with normal ophthalmic examinations weighing 568 ± 65 kg (mean ± standard deviation) and aged 11 ± 4 years were given 20 mg/kg acetaminophen orally every 12 h for a total of s...
Knych HK, Weiner D, Harrison L, McKemie DS.Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. S...
Knych HK, Mama K, Oakleaf M, Harrison LM, McKemie DS, Kass PH.The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
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Sandbaumhüter FA, Aerts JT, Theurillat R, Andrén PE, Thormann W, Jansson ET.The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was us...
Pusterla N, Vaala W, Bain FT, Chappell DE, Craig B, Schneider C, Barnett DC, Gaughan E, Papich MG.Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (Protazil) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five ...
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...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z, Graiban FM, Caveney MR, Sayed R, Kadry AM.According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. Methods: The study describes levamisole and its metabolites in thoroughbred ...
Adler DMT, Jørgensen E, Cornett C.To determine the synovial fluid (SF) concentrations of lidocaine and mepivacaine after intra-articular injection with clinically relevant doses to the distal interphalangeal (DIP), metacarpophalangeal (MCP), middle carpal (MC), and tarsocrural (TC) joint at two different time points after injection in order to be able to compare concentrations with previously established concentrations associated with cytotoxicity and antimicrobial activity. Unassigned: In the first of two experiments, 20 joints (5 MC, 5 MCP, 10 DIP joints) of five horses under general anesthesia were injected with clinically ...
Wilson KE, Bogers SH, Council-Troche RM, Davis JL.To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. Methods: Nonrandomized crossover. Methods: Six adult, Thoroughbred horses. Methods: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively. Drug administration and sample collection protocols were repeated after at least a 48 hour washout period and induction of anesthesia using xylazine/ketamine and main...
Kuroda T, Minamijima Y, Mita H, Tamura N, Fukuda K, Kuwano A, Toutain PL, Sato F.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5 mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC-MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10 mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by M...
Brewer K, Machin J, Maylin G, Fenger C, Morales-Briceño A, Tobin T.Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications...
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverag...
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 ...
Carlson A, Johnson PJ, Lei Z, Keegan KG.Soluble epoxide hydrolase (sEH) inhibitors are novel anti-inflammatory and analgesic agents that could improve pain management in horses. The objective of the present study was to evaluate the anti-nociceptive effect of a single-dose intravenous administration of the sEH inhibitor trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB) using an adjustable heart bar shoe (a-HBS) model of lameness. We hypothesized that t-TUCB would improve objective and subjective lameness measures compared to the control. Methods: Reversible lameness was induced in 8 horses for 24...
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Kuwano A, Sato F.Cephalothin (CET) concentrations in body fluids (plasma, synovial fluid, pleural fluid, peritoneal fluid, and aqueous humor) and tissue samples (bone, lung, jejunum, hoof, and subcutaneous tissue) were investigated to consider the treatment of infectious diseases in horses. CET 22 mg/kg body weight was intravenously administered to 12 horses. Samples were collected from four different horses at 1, 3, and 5 hr after administration. The CET concentration in body fluids other than aqueous humor was maintained above the MIC90 values of Streptococcus zooepidemicus and Staphylococcus aureus until 5 ...
Minuto J, Bedenice D, Ceresia M, Zaghloul I, Böhlke M, Mazan MR.Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Unassigned: To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability. Unassigned: Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respirato...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
Melo-Neto GB, Mattos LS, Alonso JM, Rosa GS, Silva JRB, Lima WF, Mendes AF, Machado VMV, Alves ALG, Watanabe MJ, Rodrigues CA, Hussni CA.No abstract available
Ekstrand C, Michanek P, Gehring R, Sundell A, Källse A, Hedeland M, Ström L.Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Unassigned: Eight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plas...
Wijekoon S, Tsogbadrakh M, Sunaga T, Wang Y, Mwale C, Kim S, Alimaa D, Okumura M.The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in to two-groups; one group was treated with a PPS once a week for 4-weeks while another group keeping as placebo. Blood samples at day 0 (D0), before race (BR; day 28) and after race (AR; day 28) were analyzed for serum biochemistry, hepcidin and iron concentrations. Significant reduction of hepcidin was observed at AR in PPS group when compared with BR placebo (P<0.05) and AR placebo (P<0.01). Mean hepcidin concentration differ...
Current drug metabolismAugust 27, 2022
Volume 23, Issue 10 850-865 doi: 10.2174/1389200223666220825093945
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported. Objective: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control. Methods: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of ful...
Knych HK, Finno CJ, Katzman S, Ryan D, McKemie DS, Kass PH, Arthur RM.Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study. Objective: (1) To determine clodronate conc...
Kellon EM, Gustafson KM.Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia...
Burroughs DL, Lorch G, Guo Y, Hill K, Schroeder EL, Cole LK, Phelps MA.Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed. Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.v.) MMF and its downstream metabolites in healthy horses. Methods: Six healthy Standardbred mares. Methods: Generic MMF (Par Pharmaceuticals; Chestnut Ridge, NY, USA) was reconstituted and admi...
Knych HK, Kanarr K, Fang Y, McKemie DS, Kass PH.To describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses. Methods: Randomized balanced crossover study. Methods: A total of seven University-owned horses, five mares and two geldings, aged 3-6 years. Methods: Horses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg), M6G (0.01 mg kg) and M3G (0.03 mg kg). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentr...
Galecio JS, Escudero E, Badillo E, Marín P.Tildipirosin is a novel semisynthetic macrolide antibiotic exclusively used in veterinary practice to treat respiratory infections. There are no pharmacokinetic or safety information available regarding the use of tildipirosin after intramuscular administration in horses. Thus, the objective of this work was to determine the disposition kinetics of tildipirosin after intravenous (IV) and intramuscular (IM) administration in horses and its potential muscle damage and cardiotoxicity. Six mature, Spanish-breed horses were used in a crossover study with a washout period of 30 days. Tildipirosin (...
Kvaternick V, Pollmeier M, Fischer J, Hanson PD.The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the eliminatio...
Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT.Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Objective: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Methods: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flun...
Sánchez de Medina A, Serrano-Rodríguez JM, Díez de Castro E, García-Valverde MT, Saitua A, Becero M, Muñoz A, Ferreiro-Vera C....Intravenous pharmacokinetics and oral bioavailability of cannabidiol (CBD) with different formulations have not been investigated in horses and may represent a starting point for clinical studies. Objective: To describe pharmacokinetics after intravenous and oral administrations with oil and micellar formulations and simulate different treatments. Methods: Single intravenous experiment and two-way randomised oral experiments, Latin-square design. Methods: Eight healthy horses received intravenous CBD at 1.00 mg/kg dose, oral CBD in sesame oil and in micellar formulation, both at 10.00 mg/k...
Thomas E, Thomas V, Wilhelm C.Cefquinome is known for its use as an antibacterial drug in cattle and pigs. The objective of this study was to evaluate the antibacterial activity of cefquinome against equine pathogenic bacteria. The minimum inhibitory concentration (MIC) of cefquinome was determined for a total of 205 strains, which had recently been isolated in Europe from diseased horses (respiratory infection, foal septicaemia). The bactericidal activity was tested against 19 strains using the time killing method. The post-antibiotic effect (PAE) and post-antibiotic sub-MIC effect (PA SME) were determined against 12 stra...
Schnepf A, Bienert-Zeit A, Ertugrul H, Wagels R, Werner N, Hartmann M, Feige K, Kreienbrock L.The usage of antimicrobial drugs (AMs) leads to an increase in antimicrobial resistance (AMR). Although different antimicrobial usage (AMU) monitoring programs exist for livestock animals in Germany, there is no such system for horses. However, with the increasing usage of electronic practice management software (EPMS), it is possible to analyze electronic field data generated for routine purposes. The aim of this study was to generate AMU data for German horses with data from the Clinic for Horses (CfH), University of Veterinary Medicine Hannover (TiHo), and in addition to show that different...
Hustace JL, Firshman AM, Mata JE.To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. Methods: 4 adult horses. Methods: 6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography. Results: Mean +/- SD distribution half-life of metformin following IV administration was 24.9 +/- 0.4 minutes with a volume of distribution of 0.3 +/- 0.1 L/kg. Mean area under the curve was 20.9 +/- 2.0 h.microg/mL for IV adminis...
Van Hoogmoed LM, Nieto JE, Snyder JR, Harmon FA.To report prokinetic strategies used to manage horses after gastrointestinal surgery. Methods: Electronic questionnaire. Methods: Diplomates of the American College of Veterinary Surgeons (ACVS) who perform equine intestinal surgery. Methods: A survey (21 questions) designed to determine use of prokinetic agents was sent electronically to 112 ACVS Diplomates known to perform equine intestinal surgery. Several clinical scenarios were also described to determine which, if any, prokinetic agent respondents would select. Results: Responses were obtained from 58 (52%) surgeons from 44 clinics. Sele...
Clarke KW, Paton BS.The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
Waters LJ, Hanrahan JP, Tobin JM, Finch CV, Parkes GMB, Ahmad SA, Mohammad F, Saleem M.Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a ...
Little D, Brown SA, Campbell NB, Moeser AJ, Davis JL, Blikslager AT.To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. Methods: 18 horses. Methods: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores...
Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S, De Backer P, Croubels S.Species differences in oral bioavailability, first-pass metabolism and pharmacokinetics of biopharmaceutics classification system (BCS) class I compound acetaminophen were studied. The absolute bioavailability was 42.2%, 39.0%, 44.5%, 75.5% and 91.0% in chickens, turkeys, dogs, pigs and horses, respectively. After hydrolysis of metabolites by beta-glucuronidase/sulfatase, apparent bioavailability increased significantly in all species (turkeys: 72.4%, dogs: 100.5%, pigs: 102.2%), except horses (91.6%). Mean metabolic ratios of [acetaminophen glucuronide]/[acetaminophen] between 0 and 1h were s...
Venner M, Kerth R, Klug E.Tulathromycin is a new injectable macrolide antibiotic used for the treatment of pulmonary diseases of swine and cattle. In this study, 37 foals with sonographic evidence of lung abscesses were treated with tulathromycin (2.5mg/kg intramuscularly [IM] once weekly, group 1) and 33 foals (group 2) with a combination of azithromycin (10mg/kg per os [PO] once daily for the first seven days of therapy, thereafter every other day) and rifampin (10mg/kg PO twice daily). The bacterial aetiological agent was not determined. The foals were only mildly sick and the median number of pulmonary abscesses wa...
Costa GL, Cristarella S, Quartuccio M, Interlandi C.To evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies. Methods: Within-subject blinded. Methods: Twenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg). Methods: On separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg(-) (R) tramadol 3 mg kg(-1) given over 15 minutes (T) or tramadol 3 mg kg(-1) followed by romifidine 50 μg kg(-1) (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation ...
Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B.Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gaba...
Guedes AGP, Aristizabal F, Sole A, Adedeji A, Brosnan R, Knych H, Yang J, Hwang SH, Morisseau C, Hammock BD.This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independe...
Valverde A, Gunkelt C, Doherty TJ, Giguère S, Pollak AS.Lidocaine constant rate infusions (CRIs) are common as an intraoperative adjunct to general anaesthesia, but their influence on quality of recovery has not been thoroughly determined. Objective: To determine the effects of an intraoperative i.v. CRI of lidocaine on the quality of recovery from isoflurane or sevoflurane anaesthesia in horses undergoing various surgical procedures, using a modified recovery score system. Objective: The administration of intraoperative lidocaine CRI decreases the quality of recovery in horses. Methods: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min...
Brophy PM, MacKintosh N, Morphew RM.Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokine...
Rezende ML, Grimsrud KN, Stanley SD, Steffey EP, Mama KR.The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations dec...
Berghaus LJ, Giguère S, Guldbech K.The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or co...
Johnson CB, Taylor PM.We have investigated in eight ponies the effects of three different end-tidal concentrations of halothane, isoflurane and methoxyflurane on median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential (DD) of the middle latency auditory evoked potential (MLAEP). The three concentrations of each agent were chosen to represent approximately the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane anaesthesia, F95 decreased progressively as halothane concentration increased, from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%...
Jamila N, Khairí·ªn M, Yeong KK, Osman H, Murugaiyah V.Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a rich source of xanthones and benzophenones. Objective: This study was aimed to isolate and characterize potential cholinesterase inhibitors from the extracts of G. hombroniana bark and investigate their interactions with the enzymes. Methods: The dichloromethane extract afforded five triterpenoids which were characterized by NMR and mass spectral techniques. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The c...
Sellon DC, Monroe VL, Roberts MC, Papich MG.To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. Methods: 10 healthy adult horses. Methods: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, a...
Werner LA, Hardy J, Bertone AL.To compare intra-articular (IA) and bone gentamicin concentrations achieved after intra-articular administration or regional intravenous perfusion (RIP). Methods: Experimental study. Methods: Twelve healthy adult horses. Methods: Horses were assigned to 2 treatment groups (n = 6/group): Group 1, 1 g gentamicin administered simultaneously in both left and right metacarpophalangeal joints and group 2, 1 g gentamicin administered simultaneously in both left and right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were collected. Gentamicin concentrations were determined by...
Okamura K, Sasaki N, Yamada M, Yamada H, Inokuma H.Although extensive work has been done to elucidate the beneficial and unfavorable effects of gastrointestinal prokinetic agents in humans, little is known on the effects of these agents in horses. In this study, we compared the effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric emptying, jejunal and caecal motility and evaluated these agents' adverse drug reactions (ADRs). Methods: Seven healthy adult Thoroughbreds. Methods: Mosapride 1.0mg/kg and 2.0mg/kg, metoclopramide 0.2mg/kg, and cisapride 1.0mg/kg were dissolved in 100mL distilled water for oral administrat...
Hamamoto-Hardman BD, Steffey EP, Weiner D, McKemie DS, Kass P, Knych HK.The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total prote...
Toutain PL, Lassourd V.The current performance of analytical techniques used for drug control in horses lead the Regulatory Authorities to decide whether trace levels of drugs legitimately used for therapeutic medication should or should not be reported. Here, we propose a well-ordered and nonexperimental pharmacokinetic/pharmacodynamic approach for the determination of irrelevant drug plasma (IPC) and urine concentrations (IUC). The published plasma clearance is used to transform an effective (marketed) dose into an effective concentration (EPC). EPC is transformed into an IPC by applying a safety factor (SF). This...
Noble G, Edwards S, Lievaart J, Pippia J, Boston R, Raidal SL.Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses. Objective: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses. Methods: Forty-nine healthy, university-owned adult lightbreed horses. Methods: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/k...
Ekman L, Nilsson G, Persson L, Lumsden JH.A method of determining the volumes of synovia in certain articular cavities in the horse is described. The method is based on the degree of dilution of human serum albumin labelled with I that is injected into the joint. It is shown that uniform distribution of the injected substance is attained within 20 min post injection. The elimination of the labelled substance was found to follow the pattern of a single exponential function. The following volumes of synovia were determined (mean ± s) : hock, 39.8 ± 2.1 ml; radio-carpal, 12.6 ±1.5 ml; intercarpal, 14.9 ± 0.6 ml; foreleg fetlock joint...
