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Topic:Intravenous Administration
Pharmacokinetics/pharmacodynamics cut-off determination for fosfomycin using Monte Carlo simulation in healthy horses. 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...
Effects of β-Glucan Supplementation on LPS-Induced Endotoxemia in Horses. β-glucan is part of the cell wall of fungi and yeasts and has been known for decades to have immunomodulating effects on boosting immunity against various infections as a pathogen-associated molecular pattern that is able to modify biological responses. β-glucan has been used in rat models and in vitro studies involving sepsis and SIRS with good results, but this supplement has not been evaluated in the treatment of endotoxemia in horses. This study aims to evaluate the effects of preventive supplementation with β-glucan in horses submitted to endotoxemia by means of inflammatory response m...
Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses. Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown. Objective: Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant-induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant-induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose-dependent manner. Methods: Eight healthy horses. Methods: Randomized placebo-controlled ...
Clinical implications of imprecise sampling time for 10- and 30-min thyrotropin-releasing hormone stimulation tests in horses. The thyrotropin-releasing hormone (TRH) stimulation test is used to diagnose pituitary pars intermedia dysfunction (PPID) using 10- or 30-min protocols. Imprecise sampling time for the 10-min protocol can lead to misdiagnoses. Objective: To determine the effect of imprecise sampling time for the 30-min protocol of the TRH stimulation test. Methods: In vivo experiment. Methods: Plasma immunoreactive adrenocorticotropin (ACTH) concentrations were measured 9, 10, 11, 29, 30 and 31 min after intravenous administration of 1 mg of TRH in 15 control and 12 PPID horses. Differences in ACTH concent...
Effect of Procaine Penicillin G and Flunixin Meglumine on Serum Amyloid A Response in Healthy Adult Horses. This study was designed to determine the effect of PPG and/or flunixin meglumine on SAA response when used at clinical dosing regimens in healthy adult horses. Six healthy adult horses were enrolled in a crossover study design including one control and three treatment groups: no treatment (control); PPG alone (intramuscularly q12h for 72h); flunixin meglumine alone (intravenously q24h for 72h); and PPG (intramuscularly q12h for 72h) and flunixin meglumine (intravenously q24h for 72h). Whole blood was collected at 0, 24, 48, 72, 96 and 120 hours post-initial drug administration to measure SAA u...
Contrast administration via ultrasound-guided injection of the cranial tibial artery results in contrast enhancement of the soft tissues of the metatarsus in horses undergoing CT. Delivery of mesenchymal stem cells (MSC) via intravascular techniques to treat diffuse and/or inaccessible soft tissue injuries has grown in popularity. The purpose of the current prospective, analytical pilot study was to utilize CT to validate this novel technique and provide additional evidence to support its use for injectate delivery to specific soft tissue structures. Of particular interest was the proximal suspensory ligament, which presents a challenging injection target. Six adult horses without lameness underwent CT of the distal hindlimbs. Scans were obtained prior to ultrasound-gui...
Ultrasonographic Assessment of Small Intestinal Motility Following Hyoscine Butylbromide Administration in Horses: A Pilot Study. Horses commonly receive hyoscine butylbromide (HB) prior to hospital admission for colic. This could alter the appearance of the small intestine (SI) on ultrasound scan and affect clinical decision making. The aim of this study was to assess the impact of HB on ultrasonographically assessed SI motility and heart rate. Six horses hospitalised for medical colic with no significant abnormalities on baseline abdominal ultrasound examination were included. Ultrasound was performed in three locations (right inguinal, left inguinal and hepatoduodenal window) before and at 1, 5, 15, 30, 45, 60, 90, an...
Transdermal Flunixin Meglumine as a Pain Relief in Donkeys: A Pharmacokinetics Pilot Study. Recent approval of transdermal flunixin meglumine (FM) (Banamine®) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine t...
Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses. Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover stu...
Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses. To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (C ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. Methods: Randomized crossover study. Methods: Seven healthy adult horses. Methods: The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. A...
Identification of erythropoietin mimetic peptide 1 linear form in a sealed vial and its administration study in horses for doping control purpose. The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis st...
Effects of calcium supplementation to resuscitation fluids in endurance horses: A randomized, blinded, clinical trial. The addition of calcium to resuscitation fluids is a common practice in horses, but studies evaluating the effects of calcium supplementation are limited. In healthy horses, decreases in heart rate and changes in serum electrolyte concentrations have been reported. Objective: Calcium gluconate administration at a rate of 0.4 mg/kg/min to eliminated endurance horses with metabolic problems will affect heart rate, gastrointestinal sounds, and serum electrolyte concentrations. Methods: Endurance horses eliminated from the Tevis Cup 100-mile (160 km) endurance ride for metabolic problems and req...
Control of a sulfadoxine/trimethoprim combination in the competition horse: Elimination, metabolism and detection following an intravenous administration. The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-...
Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses. The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a...
Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations. 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...
Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand? While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery...
Pharmacodynamics and pharmacokinetics of nalbuphine in xylazine‑sedated horses. This study describes the selected pharmacodynamics and pharmacokinetics of nalbuphine (NAL) in xylazine (XYL)‑sedated horses. Five adult healthy horses were randomly received 2 treatments at a 1‑week interval; XYL treatment (0.55 mg/kg IV) and XYL/NAL treatment (XYL, 0.55 mg/kg IV; NAL, 0.3 mg/kg IV). The measured pharmacodynamic variables were sedative and analgesic effects and the effect on ataxia and some physiological parameters. for the pharmacokinetics of NAL, its plasma concentrations were measured using HPLC and a 2‑compartment analysis was performed. Greater and prolonged sedati...
Potassium penicillin and gentamicin pharmacokinetics in healthy conscious and anesthetized horses. 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...
Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations. 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...
Cardiovascular effects of intravenous morphine in anesthetized horse. To investigate whether morphine causes a change in mean arterial blood pressure (MAP) heart rate (HR) and oxygen extraction (OE) rate in healthy horses anesthetized with isoflurane and a dexmedetomidine infusion. Unassigned: The study design was prospective clinical, randomized, blinded two groups including 33 horses. All horses were sedated with romifidine IV, and anesthesia was induced with midazolam IV and ketamine IV and maintained with isoflurane in oxygen and medical air and a dexmedetomidine infusion. As a baseline venous and arterial blood, HR and MAP were sampled. Thereafter either mo...
Pharmacokinetics of butorphanol following intravenous and intramuscular administration in donkeys: A preliminary study. 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 ...
Intravenous Magnesium Sulphate in Standing Horses: Effects on Physiological Parameters, Plasma Concentration of Magnesium and Nociceptive Threshold Tests☆. A bolus of 50 mg kg MgSO (treatment Mg) or the same volume of saline (treatment S) was infused over 15 minutes in 5 adult healthy horses. T0 was the end of the infusion. Physiological parameters were recorded throughout the study period. Measurements of electrical, thermal, and mechanical nociceptive thresholds were performed at the pelvic limbs at baseline (before T0), and at specific timepoints. Blood samples were taken at fixed timepoints before, during and until 12 hours after the infusion. For statistical analysis, the 95% confidence intervals (CI's) for the differences in nociceptive th...
Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares. 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...
Characterization of the pharmacokinetics, behavioral effects and effects on thermal nociception of morphine 6-glucuronide and morphine 3-glucuronide in horses. 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...
Pharmacokinetics of tildipirosin in horses after intravenous and intramuscular administration and its potential muscle damage. 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 (...
Effects of detomidine or romifidine during maintenance and recovery from isoflurane anaesthesia in horses. To evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia. Methods: Prospective, randomized, blinded, clinical study. Methods: A total of 63 healthy horses undergoing elective surgery during general anaesthesia. Methods: Horses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg), maintenance (40 μg kg hour) and before recovery (20 μg kg). In group D2.5, horses were given detomidine IV f...
Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses. To determine the pharmacokinetics, bioavailability, and pharmacological effects of cannabidiol (CBD) in senior horses. Methods: 8 university-owned senior horses. Methods: In this randomized, crossover study, horses were assigned to receive either a single oral dose of 2 mg/kg CBD in oil or a single IV dose of 0.1 mg/kg CBD in DMSO between August 10 and September 4, 2020. Blood samples were collected before and then 0.5, 1, 4, 8, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, and 264 hours after CBD administration. Serum biochemical analyses and CBCs were performed. Plasma concentrations of CBD ...
Use of dexmedetomidine repeated subcutaneous administration for balanced anaesthesia in horses. A balanced anaesthetic protocol is a common concept in modern veterinary anaesthesia and aims to maintain good intraoperative cardiopulmonary function. In horses, alpha-2-agonists produce sedation and analgesia and have been shown to reduce inhalational anaesthetic requirements when administered intravenously. Furthermore, these drugs can improve recovery quality. Preliminary investigations of subcutaneous dexmedetomidine administration in humans demonstrated a reduced haemodynamic impact if compared with the intravenous route suggesting that dexmedetomidine is adequately absorbed with both ad...
Preliminary study of the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of morphine 6-glucuronide (M6G) following intravenous administration to horses. Although morphine has demonstrated antinociceptive effects in horses, its administration has been associated with dose-dependent adverse effects. In humans and rats, part of the analgesic effect of morphine has been attributed to the active metabolite, morphine-6-glucuronide (M6G). Although morphine can cause several undesirable effects, M6G has a more favorable safety profile. The objective of this study was to characterize the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of M6G following intravenous administration to a small group of horses. In Part ...
