Journal of veterinary pharmacology and therapeutics.
Publisher:
Blackwell Scientific Publications.
Frequency: Bimonthly
Country: England
Language: English
Author(s):
American College of Veterinary Pharmacology & Therapeutics., Association for Veterinary Clinical Pharmacology and Therapeutics., European Association for Veterinary Pharmacology and Toxicology.
Start Year:1978 -
ISSN:
0140-7783 (Print)
1365-2885 (Electronic)
0140-7783 (Linking)
1365-2885 (Electronic)
0140-7783 (Linking)
Impact Factor
1.3
2022
| NLM ID: | 7910920 |
| (DNLM): | J41230000(s) |
| (OCoLC): | 04580359 |
| Coden: | JVPTD9 |
| Classification: | W1 JO97Q |
Plasma and Urinary Elimination Profiles of Medetomidine Metabolites in Horses for the Purpose of Doping and Medication Control. Medetomidine, an α₂-adrenergic agonist, is widely used as a sedative in horses. While its pharmacological effects are established, limited data exist on elimination of its metabolites, 3'-hydroxy medetomidine (HMD) and 3'-carboxy medetomidine (CMD), which are of regulatory interest. HMD is currently targeted in plasma and urine under International Screening Limits (ISLs) established by the International Federation of Horseracing Authorities (IFHA). In this study, seven Thoroughbreds received 6.3 μg/kg of medetomidine intravenously. Blood and urine were collected for 96 h and analyzed b...
Pharmacokinetics of Topical Administration of Altrenogest in Mares and Implications for Human Health. Altrenogest is a synthetic progestogen widely used in equine reproductive management. Adverse effects to altrenogest have been reported in people with cutaneous exposure reported as the highest exposure pathway. Despite these reports, there has been no quantitative research to determine the capacity for altrenogest to be absorbed through skin. This study aimed to determine if cutaneous application of oral altrenogest results in systemic absorption in mares and to evaluate the influence of application site. A randomized, two-period, two-treatment crossover study was undertaken in eight mares. M...
Ertapenem Pharmacokinetics in Equine Plasma and Synovial Fluid Following a Single Intravenous Dose. This study describes the pharmacokinetics of ertapenem, a carbapenem antimicrobial that has not been previously studied in equids. Administered as a 30 mg/kg intravenous bolus to six healthy horses, serial blood and synovial samples were obtained over 8 h after administration. Pharmacokinetic analysis of plasma and synovial fluid was performed. In plasma, the AUC was 353.10 h × μg/mL (CV = 49.02%), Vss 79.34 mL/kg (CV = 22.85%), CL 84.96 mL/h/kg (CV = 31.31%) and t1/2 2.03 h (CV = 15.32%). In synovial fluid, the AUC was 524.10 h × μg/mL (CV = 16.03...
Pharmacokinetics and Anti-Inflammatory Effects of Intramuscular Betamethasone in Exercised Thoroughbred Horses. The pharmacokinetics and pharmacodynamics of betamethasone following intra-articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty-four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC-MS/MS and pharmacokinetic parameters determined using a Population PK three-compartment model. The duration of pharmacodynamic effects was assessed by...
Exposure to Subcutaneously Administered Butorphanol in Horses Pre-Treated With Detomidine or Detomidine-Vatinoxan. The aim of the study was to determine the exposure to subcutaneously administered butorphanol in horses pre-treated with intravenous (IV) detomidine, with or without vatinoxan, a peripherally selective alpha-adrenoceptor antagonist. Five healthy, adult horses received three IV treatments 7 days apart, in a randomized, cross-over design: detomidine 20 μg/kg (DET-B), detomidine 20 μg/kg with vatinoxan 200 μg/kg (DETVAT-B) and saline (S-B), all followed by 0.1 mg/kg of butorphanol administered subcutaneously 30 min later. Venous samples were collected between 10 and 270 min after...
Pharmacokinetics of Intragastric Ursodeoxycholic Acid and Its Impact on Bile Acid Profiles in Horses. Ursodeoxycholic acid (UDCA), a secondary bile acid (BA) with therapeutic applications, is standard therapy for cholestatic hepatopathies in humans. In recent years, its use has been increasingly explored in equine medicine for similar indications. Pharmacokinetic data for UDCA in horses are currently lacking. This study aimed to describe the pharmacokinetic parameters following a single intragastric administration of 15 mg/kg in nine healthy, fasted horses and to characterize the changes in their BA profiles. Plasma concentrations of UDCA were measured at specific time points using liquid ch...
Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses. Pharmacokinetics (PK) of intramuscular (IM) and subcutaneous (SC) ketamine in horses has not been described. This study aimed to evaluate the PK and safety of ketamine and its metabolites after a single SC or IM administration. In Phase 1, two horses received 0.5 or 1 mg/kg of ketamine via SC and IM routes. In Phase 2, eight horses received 0.5 mg/kg IM. Plasma or serum concentrations of ketamine and major metabolites were determined by a validated liquid chromatography-mass spectrometry method at baseline and selected intervals post-administration. Subcutaneous administration resulted in ...
Plasma and Urine Pharmacokinetics of Intravenous Pridinol in Thoroughbreds for Its Medication Control. We examined the pharmacokinetics of intravenous pridinol in six thoroughbred horses. Each horse received a single 20 mg dose of pridinol mesylate via the jugular vein, and plasma and urine samples were collected over 72 h. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify pridinol concentrations in plasma and urine, allowing for the calculation of pharmacokinetic parameters. A three-compartment model best fit the plasma elimination data. Using the Toutain model, irrelevant plasma and urine concentrations were estimated to be 0.00284 and 0.000612 ng/mL, respec...
Pharmacokinetics of Remimazolam Versus Midazolam After Intravenous Administration to Horses. Remimazolam (RMZ) is a new short-half-life benzodiazepine used in humans. We compared the pharmacokinetics and sedative effects of RMZ with those of midazolam (MDZ) in Thoroughbred horses. Six Thoroughbreds received a single IV dose of RMZ 0.05 mg/kg or MDZ 0.05 mg/kg in a randomized crossover design. Blood samples were collected, and plasma RMZ and MDZ concentrations were measured by LC-MS/MS. Plasma concentrations were analyzed by using non-compartmental analysis and a nonlinear mixed effect model. The half-life of RMZ (0.77 ± 0.15 h) was significantly shorter than that of MDZ (3....
Differences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid Following Oral Administration to Horses. There has been a growing interest in the use of cannabinoids in horses in recent years. Several studies have reported on the pharmacokinetics of cannabidiol (CBD) in horses. However, cannabidiolic acid (CBDA) has received less attention, despite limited evidence suggesting clinically beneficial effects in other species. Horses were administered 3 mg/kg of CBD, 3 mg/kg of CBDA, and a placebo per os in a crossover design, with a one-week washout period between treatments. Plasma and urine samples were collected and analyzed using ultra high-performance liquid chromatography coupled to tandem...
Is Rifampin (Rifampicin) Essential for the Treatment of Rhodococcus equi Infections in Foals? A Critical Review of the Role of Rifampin. Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a "moving target" along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better ef...
Pharmacokinetics of Chloramphenicol and Chloramphenicol Glucuronide in Horses Following Administration Per Rectum or via Nasogastric Intubation. Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chl...
Penicillin and Gentamicin Concentrations in the Uterine Fluid of Non-Pregnant Mares Following a Single Intrauterine Infusion. Despite their widespread clinical use, there is limited pharmacokinetic data for many equine intrauterine antimicrobials. This study aimed to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation. We hypothesized that both formulations would result in therapeutic concentrations, with total concentrations sustained for longer using the long-acting formulation. Mares were administered 2400 mg of procaine penicillin and 200 mg of gentamicin via a single intrauterin...
Distribution of Alprazolam Into the Milk of Lactating Mares and Subsequent Absorption by Nursing Foals. Alprazolam is used to facilitate mare-foal bonding in aggressive or anxious postpartum mares. In humans, alprazolam crosses the blood-milk barrier, but the amount transferred into milk is minor and compatible with breastfeeding as the relative infant dose is < 10%. Similar data are not available for horses. The aim of this study was to measure alprazolam in serum and milk of mares (milk: serum ratio) administered alprazolam, and to determine alprazolam serum concentrations in nursing foals to estimate the extent of absorption. This was a prospective observational study involving 7 healthy...
Meta-Analysis and Mechanism-Based Modeling of Synovial and Plasma Pharmacokinetics and Adrenal Suppression Following Intra-Articular Injection of Methylprednisolone Acetate in Horses. 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...
Plasma and Urine Pharmacokinetics of Long-Acting Injectable Omeprazole Following Intramuscular Administrations to Healthy Thoroughbred Horses. Omeprazole is a gastric acid secretion inhibitor used as an effective anti-ulcer drug. Based on oral administration studies, its International Screening Limit (ISL) was established in plasma and urine at 1 ng/mL with a Detection Time (DT) of 48 h. A novel formulation of injectable omeprazole has since been released, and therefore, a pharmacokinetic study was performed to assess the DT above the ISL against current advice. Six Thoroughbred horses were given four repeated weekly intramuscular administrations of omeprazole (4 mg/kg). Plasma and urine omeprazole concentrations were measured ...
Pharmacokinetics of Salbutamol in Thoroughbred Horses After a Single Intravenous or Inhaled Administration. Salbutamol is a short-acting and selective beta-2 adrenergic agonist. Inhaled (IH) administration of salbutamol is widely used to control lower respiratory tract disease in horses. Here, we estimated the pharmacokinetic parameters of salbutamol after a single intravenous (IV) or IH administration in six horses, and we statistically analysed the detection times with various dosing regimens. Plasma and urine concentrations of salbutamol were measured by liquid chromatography-tandem mass spectrometry, and data were modelled by using a nonlinear mixed effect model followed by Monte Carlo simulatio...
Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses. Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, ...
Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrom...
Detection times of clodronic acid in horses with orthopedic disease. Clodronic acid is designated as a controlled medication for competition horses by the International Federation for Equestrian Sports and, according to the International Federation of Horseracing Authorities, clodronic acid is not to be administered to racehorses younger than 3.5 years or within 30 days prior to a race. In this study, 35 horses involved in competition were treated with a single dose of 1.53 mg clodronic acid/kg bodyweight intramuscularly. Plasma samples were obtained before treatment and 10, 20, 30, and 40 days post-administration. Clodronic acid concentrations were mea...
Population pharmacokinetics of butorphanol following intramuscular administration to exercised thoroughbred horses. Butorphanol is commonly administered, both by the intravenous and intramuscular routes, to racehorses to facilitate handling for diagnostic procedures. As the administration of butorphanol for therapeutic purposes is considered appropriate, in order to avoid inadvertent positive drug tests, a thorough understanding of the pharmacokinetics of this drug is necessary. In the current study, 12, exercised Thoroughbred horses were administered a single intramuscular dose of 0.1 mg/kg butorphanol, and serum and urine samples were collected at various times post drug administration for determination...
The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses. Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. ...
Effect of clodronate on gene expression in the peripheral blood of horses. There are two FDA-approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated...
Evaluation of plasma and urine pharmacokinetics of tranexamic acid for equine medication control. This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain mo...
A review of current chemistry, pharmacology, and regulation of endogenous anabolic steroids testosterone, boldenone, and nandrolone in horses. Anabolic androgenic steroids are synthetic substances related to the male sex hormones (androgens). These agents promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). Anabolic steroids have been illegally used for many years as performance-enhancing drugs in human, equine, and canine sports and as growth promoters in livestock reared to provide meat for human consumption. The analytical challenge to developing effective means of control within these fields has been exacerbated by the reported endogenous nature of some ...
Novel holistic pharmacokinetic model applied to plasma and urine concentrations of 2,5-dihydroxybenzene sulphonate following administrations of calcium dobesilate and etamsylate to exercised horses. Calcium dobesilate (CD) is a synthetic venoactive drug used in veterinary medicine to treat equine navicular disease. Etamsylate is a haemostatic agent used in horses for the treatment of exercise-induced pulmonary haemorrhage. Both etamsylate and CD dissociate in the circulatory system with 2,5-HBSA as the active drug. The aim of the research was to be able to provide detection time (DT) advice from pharmacokinetic (PK) studies in Thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Two (pilot stud...
Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses. Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Pharmacokinetics of aminocaproic acid in thoroughbred horses. The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administere...
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 of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis. The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) ...