Topic:Pharmacokinetics
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.
[Antidoping rules in equine sports and pharmacological aspects of rule-consistent medical treatment and feeding of sport horses]. Veterinarians play an essential role in the prevention of doping in equine sports, both as attending clinicians as well as official competition veterinarians. This complex task requires comprehensive knowledge concerning the pertinent regulations. These include official laws, such as the animal protection and medicines laws as as well as rules issued by the responsible equine sports authority. Furthermore, veterinarians are required to determine adequate withdrawal times following the legitimate use of medications in sport horses. This may be performed by applying appropriate data published by...
Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses. To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration. Methods: Prospective experimental study. Methods: A total of 12 Thoroughbred horses, nine geldings and three mares, aged 4-8 years. Methods: Horses were administered codeine (0.6 mg kg) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography-mass spectrometry, and plas...
Multicenter Placebo-Controlled Randomized Study of Ethyl Pyruvate in Horses Following Surgical Treatment for ≥ 360° Large Colon Volvulus. Identifying therapies that mitigate ischemic colonic injury and improve mucosal healing and intestinal viability are crucial to improving survival in horses with ≥360° large colon volvulus (LCV). Ethyl pyruvate is the ethyl ester of pyruvate with diverse pharmacologic effects that limit ischemic injury and hasten intestinal mucosal repair in preclinical rodents, sheep and swine models. The objective of this study was to determine the effects of ethyl pyruvate on systemic indices of colon viability, expression of inflammatory genes in whole blood, morbidity and survival after surgical correc...
Pharmacokinetics and anti-inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses. Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objective: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. M...
Effects of coadministration of corn oil and ponazuril on serum and cerebrospinal fluid concentrations of ponazuril in horses. Ponazuril is used for the treatment of equine protozoal myeloencephalitis (EPM). Coadministration of ponazuril with oil could result in higher serum and cerebrospinal fluid (CSF) concentrations of ponazuril. Objective: Coadministration of corn oil will result in higher serum and CSF concentrations of ponazuril than when ponazuril is administered alone. Methods: Ten resident university-owned adult horses of either sex and >2 years of age. Methods: Cohort study. Ponazuril oral paste (5 mg/kg BW; ponazuril treatment group (PON); n = 5), or ponazuril oral paste (5 mg/kg BW; ponazuril and oil tre...
Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies. Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrati...
Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses. To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Investigation of plasma concentrations of paracetamol, metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography-electrospray ionisation-tandem mass spectrometry. Paracetamol is used widely as an over-the-counter analgesic and antipyretic medication for humans, but not for Japanese racehorses. Paracetamol can be an environmental substance, and is found together with its two isomers, metacetamol and orthocetamol, in equine urine. However, the sources and routes of paracetamol exposure remain unclear. To control the misuse of paracetamol, it is appropriate to establish residue limits for paracetamol to differentiate the administration of paracetamol from its environmental levels. In this study, we developed and validated a quantitative method for paraceta...
Pharmacokinetics of low-dose methotrexate in horses. This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concen...
Preconditioning with lidocaine and xylazine in experimental equine jejunal ischaemia. Pharmacological preconditioning of dexmedetomidine on small intestinal ischaemia/reperfusion injury has been reported in different animal models including horses. Objective: The objective was to assess if xylazine and lidocaine have a preconditioning effect in an experimental model of equine jejunal ischaemia. Methods: Terminal in vivo experiment. Methods: Ten horses under general anaesthesia were either preconditioned with xylazine (group X; n = 5) or lidocaine (group L; n = 5). A historical untreated control group (group C; n = 5) was used for comparison. An established experimental mo...
Intratesticular mepivacaine versus lidocaine in anaesthetised horses undergoing Henderson castration. In horses undergoing castration, direct comparison of intratesticular lidocaine vs mepivacaine as analgesic adjuncts has not yet been analysed. Objective: To compare the effects of intratesticular lidocaine and mepivacaine during equine castration using the Henderson drill under total intravenous anesthesia. Methods: Randomised, double-blinded clinical study. Methods: Thirty-four stallions were anaesthetised using xylazine-ketamine and randomly selected to receive 10 mL either lidocaine or mepivacaine injected into each testicle. Both surgeon and anaesthetist were blinded to the selected trea...
Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial ...
Pharmacokinetics of three formulations of vitacoxib in horses. The pharmacokinetic properties of three formulations of vitacoxib were investigated in horses. To describe plasma concentrations and characterize the pharmacokinetics, 6 healthy adult Chinese Mongolian horses were administered a single dose of 0.1 mg/kg bodyweight intravenous (i.v.), oral paste, or oral tablet vitacoxib in a 3-way, randomized, parallel design. Blood samples were collected prior to and at various times up to 72 hr postadministration. Plasma vitacoxib concentrations were quantified using UPLC-MS/MS, and pharmacokinetic parameters were calculated using noncompartmental analysis...
A comparative study on the equine and camelid antivenoms upon cardiovascular changes induced with Hemiscorpius lepturus venom in rats. In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by venom in rats. Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 µl) were given intravenously in 10 min before venom injection (400 µg/rat). The neutralizing potencies of camelid and equi...
Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation. In metabolically stable horses, alpha-2-agonists suppress insulin secretion with transient hyperglycemia and rebound hyperinsulinemia. In horses with insulin dysregulation (ID), the effect of alpha-2-agonists has not been investigated; however, both the alpha-2-agonist-induced suppression of insulin secretion and rebound hyperinsulinemia could have clinical relevance. Objective: In horses with ID, alpha-2-agonists will alter insulin and glucose dynamics. Methods: Seven horses with ID and 7 control horses. Methods: In this randomized crossover study, xylazine hydrochloride (1.1 mg/kg) or detomi...
Systemic and local effects of lidocaine or mepivacaine when used for intravenous regional anaesthesia of the distal limb in standing sedated horses. Local anaesthetics are being combined clinically with amikacin in intravenous regional limb perfusion (IVRLP), with limited knowledge on the analgesia provided and its onset and duration of action after tourniquet application and release. Objective: To evaluate the systemic clinical effect, limb withdrawal to nociceptive stimulation, and plasma and synovial fluid concentrations after IVRLP with lidocaine or mepivacaine in standing sedated horses. Methods: Prospective, controlled, randomised, cross-over study. Methods: Six healthy adult horses were sedated and received IVRLP with lidocaine, mep...
Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine. Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer-reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses. Objective: Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. Methods: Experimental study with repeated measures. Methods: Six healthy adult h...
Pharmacokinetics of multiple doses of chloramphenicol in fed adult horses. To the authors' knowledge, there have been no studies evaluating the pharmacokinetics of chloramphenicol administered orally to horses at the currently recommended dose of 50 mg/kg PO q6 h for multiple days. The published antimicrobial susceptibility breakpoint is 8.0 ug/mL; it is unknown if this concentration is achievable at the recommended dose rate in horses. The aim of this prospective multi-dose pharmacokinetic study was to perform pharmacokinetic analysis of chloramphenicol after multiple doses. The authors hypothesize that the antimicrobial susceptibility breakpoint will not be reached...
Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses. The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concent...
Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses. In humans, gabapentin an analgesic, undergoes non-proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses. Objective: Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses. Methods: Nine clinically healthy adult Arabian and Quarter Horses....
Methyl-coenzyme M Reductase (MCR) Receptor as Potential Drug Target for Inhibiting Methanogenesis in Horses Using Moringa oleifera L.: An in Silico Docking Study. Methane (CH) emission from nonruminant livestock, particularly equines, is a colossal burden for veterinarians worldwide. In view of this, the present context was investigated to predict the antimethanogenic attributes of Moringa oleifera L. associated phytocomponents by targeting methyl-coenzyme M reductase (MCR) receptor in horses using in silico tools. Initially, the pharmacokinetics and ADME (absorption, distribution, metabolism, and excretion) properties of 26 phytocomponents were analyzed using Lipinski's rule of five and Swiss ADME tool, respectively. Among all the tested phytocomponent...
The intravenous pharmacokinetics of butorphanol and detomidine dosed in combination compared with individual dose administrations to exercised horses. In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentratio...
Detection and Pharmacokinetics of Etoricoxib in Thoroughbred Horses. Etoricoxib, a selective inhibitor of cyclooxygenase-2, is used in the treatment of many inflammatory diseases and dental pain in humans. The aim of this study was to determine the pharmacokinetics and metabolism of etoricoxib in horses. Six horses weighing an average of 475 ± 25 kg were administered a single oral dose of etoricoxib at 1 mg/kg body weight. The results show that the drug reached a maximum concentration of 505.2 ± 67.8 ng/mL in 48 minutes after administration. The elimination half-life was calculated to be 10.20 ± 1.30 hours. Mass spectrometric analysis confirmed that eto...
Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration. Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictab...
Administration study of recombinant human relaxin-2 in horse for doping control purpose. The insulin-like peptide relaxin (RLX), an endogenous peptide hormone produced in human for pregnancy and reproduction, is also known to exert a range of physiological and pathological effects. Its use is banned in human sports, horseracing, and equestrian competitions due to its potential performance enhancing effect through vasodilation resulting in the increase of blood and oxygen supplies to muscles. Little is known about the biotransformation and elimination of RLX in horses. This paper describes an administration study of rhRLX-2 and its elimination in horses, and the development of sens...
Diclofenac Prodrugs for Intra-articular Depot Injectables: In Vitro Hydrolysis and Species Variation. Intra-articular depot injectables based on in situ suspension formation of ester prodrugs of nonsteroidal anti-inflammatory drugs are promising for management of joint pain. As candidates for this delivery approach, 5 diclofenac ester prodrugs comprising different imidazole-containing promoieties were synthesized and their physicochemical properties characterized. In vitro hydrolysis rates were investigated in buffer solutions, in 40% (v/v) human, equine, canine, and rat plasma, and in 80% (v/v) human and equine synovial fluid. Bioconversion of the prodrugs to diclofenac was found to be enzym...
Development and validation of a chiral LC-MS method for the enantiomeric resolution of (+) and (-)-medetomidine in equine plasma by using polysaccharide-based chiral stationary phases. The detection and separation of medetomidine enantiomers from the complex biological matrices poses a great analytical challenge, especially in the field of forensic toxicology and pharmacology. Couple of researchers reported resolution of medetomidine using protein-based chiral columns, but the reported method is quiet challenging and tedious to be employed for routine analysis. This research paper reported a method that enables the enantio-separation of medetomidine by using polysaccharide cellulose chiral column. The use of chiralcel OJ-3R column was found to have the highest potential for ...
Pharmacopuncture Analgesia Using Flunixin Meglumine Injection into the Acupoint GV1 (Ho Hai) After Elective Castration in Horses. The study evaluated the effect of a 1/10 dose of flunixin meglumine administered into the governing vessel 1 (GV1) acupoint in horses that underwent castration. Twenty animals received 0.02 mg/kg detomidine intravenously, followed by 2.2 mg/kg ketamine and 0.1 mg/kg diazepam by the same route, and also a local anesthesia with 30 mL lidocaine. As postoperative analgesia, the animals received 1.1 mg/kg flunixin meglumine IV (FIV) or 0.11 mg/kg flunixin meglumine into the GV1 acupoint (FGV). Behavioral parameters were assessed 12 hours before the procedure (baseline) and at 4, 6, 12, and 2...
Structural investigations of stereoselective profen binding by equine and leporine serum albumins. Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three pro...
Effect of 3% chloroprocaine hydrochloride when used for median and ulnar regional nerve blocks in lame horses. To assess onset of analgesia for 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when used for median and ulnar nerve blocks in lame horses. Methods: 6 naturally lame horses. Methods: A crossover experiment was conducted. Horses were assigned to 1 of 2 treatment groups (3% chloroprocaine or 2% mepivacaine first). Median and ulnar nerve blocks were performed in the lame limb with the assigned treatment. Lameness was objectively evaluated before treatment administration and at various points for 120 minutes after treatment with a wireless inertial sensor-based motion analysis sy...