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 |
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 5Â 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 10Â mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by M...
Control of ticks on horses using abamectin-impregnated ear tags. A pharmacokinetic and pharmacodynamic study. Several different tick species are known to infest horses. Aside from causing serious health and welfare issues, including anaemia, ill thrift, and immunosuppression, ticks can transmit a variety of important, sometimes zoonotic, pathogens. The successful prevention and treatment of tick infestations have been described, but the information is scarce and, in many instances, anecdotal. Here we describe a practical and affordable prevention of tick infestation by using abamectin-impregnated cattle ear tags affixed to a safety collar. We have assessed the radial distribution of abamectin by analy...
Pharmacokinetics of grapiprant and effects on TNF-alpha concentrations following oral administration to horses. Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses...
Pharmacokinetics of glaucine after intravenous and oral administrations and detection of systemic aporphine alkaloids after ingestion of tulip poplar shavings in horses. Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( ) and beta ( ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( ) was ...
Concentration of amikacin sulphate in synovial fluid when given in combination with dexamethasone phosphate in intravenous regional limb perfusion in standing horses. Eight horses underwent IVRLP at two occasions through a 23-gauge 2Â cm long butterfly catheter. Regional anaesthesia of the ulnar, median and medial cutaneous antebrachial nerves was performed prior, and an 8Â cm rubber tourniquet was placed on the proximal radius for 30Â minutes following the infusion. The first infusion consisted of 2Â g of amikacin sulphate and 10Â mg of dexamethasone phosphate diluted with 0.9% NaCl to a total volume of 100Â ml. The second perfusion was performed after a 2-week washout period, the same protocol was used but without dexamethasone phosphate. Synovial fluid s...
Pharmacokinetics of a single dose of oclacitinib maleate as a top dress in adult horses. The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528Â kg were administered a single dose of 0.5Â mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15Â min, 30Â min, 45Â min, 1, 2, 4, 6, 8, 12, 24, 48, and 72Â h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean C was 486Â ng/ml (range 423-549Â...
Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses. Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non-fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1Â mg/kg intravenously, 1Â mg/kg intragastrically, and 5Â mg/kg...
Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses. Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04Â mg/kg) and PO (6Â mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72Â h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics w...
Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration. Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood ...
In vivo joint synovial fluid disposition of a novel sustained-release formulation of diclofenac and hyaluronic acid in horses. Intra-articular administration of sustained-release anti-inflammatory drugs is indicated in horses suffering from joint inflammation, but no such drugs are labelled for veterinary use. To obtain initial data on synovial disposition and safety of a new sustained-release formulation of diclofenac (SYN321) in the joints of horses, an experimental interventional study of elimination and side effects of intra-articular administration of SYN321 was conducted. Nine clinically sound horses were included in the study, and SYN321 was administered by the intra-articular route. Dose ranges and sampling in...
Pharmacokinetics of fluoxetine in horses following oral administration. This study aimed to investigate pharmacokinetics of fluoxetine in horses and validate a method for liquid chromatography mass spectrometry analysis of serum levels. Fluoxetine pharmacokinetics were determined using 10Â healthy, adult horses. Fluoxetine pharmacokinetics following a single oral dose (0.25Â mg/kg) were determined using blood samples collected prior to and at several time points over 7Â days following administration. Serum concentrations of fluoxetine and its bioactive metabolite norfluoxetine were measured using liquid chromatography coupled to an accurate mass/high-resolution ma...
Pharmacokinetics of paracetamol in the Thoroughbred horse following an oral multi-dose administration. Paracetamol is a widely used, non-opioid analgesic and antipyretic drug. Scientific evidence suggests that it is an effective pain treatment in equine medicine. However, there is very little published information about the pharmacokinetics of the drug in the horse. The aim of the research was to determine the pharmacokinetics of paracetamol in equine plasma and urine to inform treatment of Thoroughbred racehorses. In this multi-dose study, paracetamol was administered orally at 20Â mg/kg to six Thoroughbred horses. Pre- and post-administration urine and plasma samples were collected and analys...
Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses. Hydroxyzine and cetirizine are first- and second-generation oral antihistamine drugs, respectively, used to treat allergic reactions in horses. Cetirizine is also a metabolite of hydroxyzine, which may lead to complexities in regulating their use in equine sporting events. The aim of the research was to be able to provide detection times (DT) from pharmacokinetic studies in thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Six and two horses were given 9 repeated administrations of hydroxyzine HC...
Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses. Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methylamino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus caballus) using a cross-over study design. The plasma samples were extracted by solid-phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high...
Pharmacokinetics of thiamine (vitamin B1) in adult horses after administration of three single intravenous doses. Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20Â mg/kg IV. Blood was collected immediately prior to drug administration and at several time poi...
Pharmacokinetic properties of metamizole active metabolites in Northeastern Brazilian donkeys (Equus asinus). Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M ) and 25 mg/kg (M ) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma ...
Pharmacokinetics of dipyrone in horses: A multi-dose, dose escalation study. Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30Â mg/kg q8h, 30Â mg/kg q12h, 60Â mg/kg q8h, and 90Â mg/kg q12h]) and treated for nine consecutive da...
Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses. Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500Â mg and blood and urine samples collected for up to 96Â h post-administration. Serum for determination of thromboxane concentrations and whole blood samp...
Pharmacodynamics and plasma concentrations of dexmedetomidine with or without vatinoxan as a constant-rate infusion in horses anaesthetized with isoflurane-A pilot study. The aim was to determine the effects of vatinoxan on dexmedetomidine plasma concentrations and effects on cardiovascular and intestinal tissue pharmacodynamics. In a prospective randomized study, six horses were premedicated intravenously with dexmedetomidine 3.5 µg kg followed by a constant-rate infusion of 7 µg kg  h (group DEX) and six horses with dexmedetomidine of the same dose (bolus and constant-rate infusion) combined with vatinoxan 130 µg kg followed by 40 µg kg  h (group VAT). Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane. Venous bloo...
Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control. In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6Â horses was conducted using a single intravenous (...
Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcusequi subsp. zooepidemicus infection model in horses. The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was samp...
Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses. Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09Â mg/kg) and oral (1Â mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liq...
Pharmacokinetics and pulmonary distribution of Draxxin® (tulathromycin) in healthy adult horses. The objective of this study was to determine the pharmacokinetics and tolerability of tulathromycin (Draxxin ; 2.5Â mg/kg once) after intramuscular (IM), subcutaneous (SC), and slow intravenous (IV) administration to six adult horses. A three-phase design and 4-week washout period were used. Drug concentrations in blood and bronchoalveolar lavage (BAL) samples were determined by ultra-performance liquid chromatography tandem mass spectrometry and pharmacokinetic parameters calculated using noncompartmental analysis. Following SC and IM administration, all horses exhibited sweating, discomfort,...
Equine antimicrobial therapy: Current and past issues facing practitioners. Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence-based clinical decision-making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra-label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. P...
Pharmacokinetics and bioavailability of tildipirosin following intravenous and subcutaneous administration in horses. This study was designed to investigate the safety and pharmacokinetic (PK) profile of tildipirosin in horses after intravenous (i.v.) and subcutaneous (s.c.) injection of a single dose at 4Â mg/kg of body weight (b.w.). A total of 12 healthy mixed breed horses were used in the study. Horses were monitored for systemic and local adverse effects, and whole blood samples were collected for hematology and plasma biochemistry analysis at time (0) and at 6, 24, and 72Â h after drug administration. For PK analysis, blood samples were collected at pre-determined times before and after tildipirosin adm...
Pharmacokinetics and pharmacodynamics of intravenous continuous rate infusion and repeated intramuscular administration of dexmedetomidine in standing horses. An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005Â mg/kg followed by a CRI at 0.01Â mg/kg/h for 15Â min then 0.005Â mg/kg/h for 60Â min) and the IM group (dexmedetomidine at 0.01Â mg/kg, followed by 0.005Â mg/kg in 30-min intervals for 60Â min). Clearance and...
Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration. Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidim...
Bayesian-based withdrawal estimates using pharmacokinetic parameters for two capsaicinoid-containing products administered to horses. Capsaicinoids deter horses from chewing on bandages and are applied topically to provide analgesia to musculoskeletal injuries. They are banned during competition due to their nerve blocking properties. The pharmacokinetics of oral (PO) and direct gastric administration via nasogastric tube (NG), or topical (TOP) administration of two capsaicinoid-containing products were investigated, and the withdrawal times required prior to competition were estimated. Capsaicin (CAP) and dihydrocapsaicin (DCAP) were quantified in plasma, and both compounds were best described by a delayed absorption two co...
The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses. The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2Â mg/kg body weight. Blood samples were collected for 96Â hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high-performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90Â min after ivermectin administration and was...
Concentration profiles and safety of topically applied betulinic acid and NVX-207 in eight healthy horses-A randomized, blinded, placebo-controlled, crossover pilot study. The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-d...