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Topic:Biological Half-Life
Biological half-life refers to the time required for a substance to decrease by half in its concentration within the body. In horses, understanding the biological half-life of various substances, such as medications, nutrients, or toxins, is important for determining dosing schedules, withdrawal times, and potential effects on equine health. The biological half-life can vary significantly depending on the substance in question, as well as factors such as the horse's metabolism, age, and health status. This page compiles peer-reviewed research studies and scholarly articles that explore the biological half-life of different substances in horses, examining factors that influence these rates and their implications for veterinary medicine and equine management.
Evidence of five digits in embryonic horses and developmental stabilization of tetrapod digit number. Previous work comparing the developmental mechanisms involved in digit reduction in horses with other mammals reported that horses have only a 'single digit', with two flanking metapodials identified as remnants of digit II and IV. Here we show that early embryos go through a stage with five digit condensations, and that the flanking splint metapodials result from fusions of the two anterior digits I and II and the two posterior digits IV and V, in a striking parallel between ontogeny and phylogeny. Given that even this most extreme case of digit reduction exhibits primary pentadactyly, we re...
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...
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...
Clock Genes Expression in Peripheral Leukocytes and Plasma Melatonin Daily Rhythm in Horses. In mammals, behavioral and physiological processes display 24-hour rhythms that are regulated by the circadian system. In the present study, we investigated clock gene expression in peripheral leukocytes in horses. For this purpose, 10 Italian Saddle gelding horses (9-11 years old; 475 ± 28 Kg) were housed in individual boxes under natural photoperiod and natural environmental temperature. Blood samples were collected at 4-hour intervals over a 48-hour period. The day before the start of sampling, left jugular furrow of each horse was cannulated for the blood sample collection performed in ...
Re-evaluation of the pharmacokinetics of xylazine administered to Thoroughbred horses. Xylazine is widely used worldwide as a short-acting sedative in general equine and racing practice. In the UK, although it has a legitimate use during training, equine anti-doping rules state it is a prohibited substance on race day. The aim of the study was to produce a detection time (DT) to better inform European veterinary surgeons so that xylazine can be used appropriately under regulatory rules. Previous publications have various limitations pertaining to analysis method, particularly for plasma and limited length of time of sample collection. In this study, pharmacokinetic data were pro...
Single-dose pharmacokinetics of orally and rectally administered misoprostol in adult horses. To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses. Methods: 8 healthy adult horses. Methods: In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured. Results: Mean maximum plasma concentr...
Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses. Hydroxyzine is a first-generation antihistamine and cetirizine, a second-generation antihistamine and active metabolite of hydroxyzine. Hydroxyzine is commonly used in performance horses and as such its use in closely regulated; however, there are no published studies suitable for establishing appropriate regulatory recommendations. In the current study, 12 exercised Thoroughbred research horses received a single oral administration of 500 mg of hydroxyzine. Blood and urine samples were collected prior to and up to 96 hr postdrug administration and concentrations of hydroxyzine and cetirizin...
Plasma concentrations of steroid precursors, steroids, neuroactive steroids, and neurosteroids in healthy neonatal foals from birth to 7 days of age. Transient hypothalamic-pituitary-adrenal axis dysfunction occurs in critically ill foals with sepsis and neonatal maladjustment syndrome (NMS). Cortisol is the most commonly measured steroid. However, a complex interaction of various steroid compounds might play a role in pathophysiology of this disorder. Objective: To identify steroid compounds present at high concentrations at birth that rapidly and steadily decrease within the first 7 days of life in healthy foals and that might be supportive diagnosis of NMS and other neonatal disorders. Methods: Ten healthy neonatal Quarter Horse foals ...
Pharmacokinetics and pharmacodynamics of olopatadine following administration via nasogastric tube to healthy horses. To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube. Methods: 4 healthy adult Thoroughbreds. Methods: Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios we...
Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses. The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples ...
Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance. Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace throughout the world in nematode parasites of small ruminants and is of increasing concern in horses, cattle, dogs and other animals. It is suspected in Onchocerca volvulus in humans. In most animals, resistance first arose to the avermectins, such as ivermectin (IVM), and subsequently to...
Pharmacokinetics of single doses of maropitant citrate in adult horses. The neurokinin-1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under-recognized in horses. Use of NK-1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC-MS/MS. Pharmacokinetic pa...
Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations. Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine-approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenico...
Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation. To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation. Methods: Experimental using six Standardbred mares. Methods: Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry. Results: Maximum plasma concentrations (t ) were reached by the earliest detection point (...
Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses. There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. Objective: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. Methods: Pharmacokinetic study, multiple dose safety study. Methods: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Seri...
Clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses premedicated with medetomidine and midazolam. To investigate the clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses, seven Thoroughbred horses were randomly anaesthetised twice with either 1 or 2 mg/kg of intravenous alfaxalone after premedication with medetomidine (6 µg/kg intravenous) and midazolam (20 µg/kg intravenous). Blood samples were collected at predetermined time points up to two hours after administration. Plasma alfaxalone concentrations were quantified by a liquid chromatography tandem-mass spectrometry method and analysed by non-compartmental pharmacokinetic analy...
Pharmacokinetics of meloxicam after oral administration of a granule formulation to healthy horses. Nonsteroidal anti-inflammatory drugs are administered in horses for several systemic diseases. Selective cyclooxygenase-2 inhibitors are preferred because of lower risk of adverse effects. Several meloxicam formulations have been tested in horses, but a recently marketed granule oral formulation has not been studied. Objective: To characterize the pharmacokinetics of a novel granule meloxicam formulation in fasted and fed horses, and to compare pharmacokinetic features with oral suspension and tablets. Methods: Seven healthy adult horses. Methods: Meloxicam was administered at 0.6 mg/kg in fas...
Pharmacokinetics and pharmacodynamics of pergolide mesylate after oral administration in horses with pituitary pars intermedia dysfunction. Published information on the pharmacokinetic and pharmacodynamic properties of pergolide is limited. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of oral pergolide in horses with pituitary pars intermedia dysfunction (PPID). The study design was a nonrandomized clinical trial. Six horses with PPID diagnosed by thyrotropin-releasing hormone (TRH) stimulation tests received pergolide at 4 μg/kg for 18 d. Plasma samples for determination of pergolide and ACTH concentration were collected 0.5 h before and 2 and 12 h after each administration of p...
Serum amyloid A in equine health and disease. Serum amyloid A (SAA) is the major acute phase protein in horses. It is produced during the acute phase response (APR), a nonspecific systemic reaction to any type of tissue injury. In the blood of healthy horses, SAA concentration is very low, but it increases dramatically with inflammation. Due to the short half-life of SAA, changes in its concentration in blood closely reflect the onset of inflammation and, therefore, measurement of SAA useful in the diagnosis and monitoring of disease and response to treatment. Increases in SAA concentration have been described in equine digestive, reprodu...
Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration. Horses with inflammatory and infectious disorders are often treated with injectable heparin anticoagulants to prevent thrombotic complications. In humans, a new class of direct oral acting anticoagulants (DOAC) appear as effective as heparin, while eliminating the need for daily injections. Our study in horses evaluated apixaban, a newly approved DOAC for human thromboprophylaxis targeting activated factor X (Xa). Our goals were to: (1) Determine pharmacokinetics and pharmacodynamics of apixaban after oral (PO) and intravenous (IV) administration in horses; (2) Detect any inhibitory effects of...
Metabolism and elimination of the catechol-o-methyltransferase inhibitor tolcapone in the horse. The metabolism of the masking agent tolcapone in the horse has been investigated. This substance was found to have undergone various chemical transformations that produced a large variety of phase I metabolites, as well as glucuronide and sulfate conjugation. Confirmation of the presence of tolcapone and the 3-O-methylated metabolite in the blood samples collected up to 240 minutes and in urine obtained up to 24 hours, was successfully conducted using both gas chromatography- and liquid chromatography-tandem mass spectrometry techniques. The 3-O-methyl tolcapone is the better marker to use i...
The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses. Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses. Methods: Masked, randomized, cross-over, Latin square design. Methods: A group of eight healthy adult horses METHODS: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg (LD), 0.04 mg kg (MD), 0.08 mg kg (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental ...
Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days. The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal hal...
Alfaxalone for total intravenous anaesthesia in horses. To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period. Methods: Prospective, experimental study. Methods: Eight Standardbred horses. Methods: Horses were premedicated with IV acepromazine (0.03 mg kg) and xylazine (1 mg kg) and anaesthesia was induced with guaifenesin (35 mg kg) and alfaxalone (1 mg kg). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a ...
Pharmacokinetics of Intrarectal Altrenogest in Horses. Hospitalized pregnant mares being held nil per os (PO) because of medical or surgical events present a dilemma for pregnancy maintenance therapy, which commonly includes oral altrenogest. Rectal administration of medications is a recognized route for achieving systemic concentrations, but there are no data on the pharmacokinetics of rectal altrenogest administration in horses. The purpose of this study was to determine the pharmacokinetics of altrenogest following PO or per rectum (PR) administration in mares. Using a randomized two-way crossover study design, six horses received altrenogest (...
Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine following intra-articular administration of a liposomal formulation to horses. The use of intra-articular (IA) local anaesthetics has proven to be an effective means to treat post-operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra- and peri-articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long-term analgesic effects) has not been evaluated in horses. Objective: Describe bupivacaine concentrati...
Evaluation of pharmacokinetic properties of vitacoxib in fasted and fed horses. The pharmacokinetic properties of vitacoxib have not been established completely; current dosage recommendations are based on clinical experiences. The primary objective of this study was to describe plasma concentrations and characterize the pharmacokinetics of vitacoxib formulation following oral administrations in horses. Also, the effect of the state of stomach contents on the absorption of vitacoxib was investigated in fed/fasted horses. Blood samples were collected prior to and at various times up to 72 hr post-administration. Drug concentrations were measured using ultra high-performan...
Rectal administration of metronidazole with and without rectal evacuation prior to use in horses. In a randomized crossover design study, 10 adult horses were administered crushed metronidazole tablets rectally at 20 mg/kg. Horses' rectums were either evacuated (E) or not evacuated (NE) of manure prior to the administration of the drug. Serum samples were taken over 24 hr and plasma concentrations were determined via high pressure liquid chromatography. At 15 min post-administration, group E had a significantly higher plasma concentration (p = 0.027), but there were no concentration differences at any other time points. There was large variability in relative bioavailability in the NE...
Time required to achieve maximum concentration of amikacin in synovial fluid of the distal interphalangeal joint after intravenous regional limb perfusion in horses. OBJECTIVE To determine the maximum concentration (Cmax) of amikacin and time to Cmax (Tmax) in the distal interphalangeal (DIP) joint in horses after IV regional limb perfusion (IVRLP) by use of the cephalic vein. ANIMALS 9 adult horses. PROCEDURES Horses were sedated and restrained in a standing position and then subjected to IVRLP (2 g of amikacin sulfate diluted to 60 mL with saline [0.9% NaCl] solution) by use of the cephalic vein. A pneumatic tourniquet was placed 10 cm proximal to the accessory carpal bone. Perfusate was instilled with a peristaltic pump over a 3-minute period. Synovial ...
