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 |
Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse. The gene and protein expression and the cellular localization of the ABC transport proteins breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2) have been examined in the intestines, liver and kidney in horse. High gene and protein expression of BCRP and MRP2 were found in the small intestines, with cellular localization in the apical membranes of the enterocytes. In the liver, MRP2 was present in the bile canalicular membranes of the hepatocytes, whereas BCRP was localized in the cytoplasm of hepatocytes...
Efficacy of intramuscular polysulfated glycosaminoglycan in a controlled study of equine carpitis. Twelve healthy horses were subject to the monoioidoacetate (MIA) carpitis model, which was allowed to develop for 7 days. The horses were then randomly divided into two groups. Group A (control) received an intramuscular injection of normal saline every 4 days for a total of seven injections while group B received 500 mg of a PSGAG (SYNTEX CSY36) intramuscularly every 4 days for seven treatments. Efficacy of the PSGAG was evaluated by three clinical outcomes: lameness score, carpal circumference and maximum carpal flexion. Clinical outcomes were measured on days -8 (previous to carpitis induct...
Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6-10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was u...
Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares. Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg/kg bodyweigh...
Patient variation in veterinary medicine: part I. Influence of altered physiological states. In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter...
Age-related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes. Time- and concentration-related actions of lipopolysaccharide (LPS) on the synthesis of prostaglandin E(2) (PGE(2)) were investigated in cartilage explants and synoviocytes harvested from 3 age groups of horses, all with clinically normal joint function: group A 20 years. Cartilage explants from group A horses were least and those from group C were most sensitive to LPS. Significant increases in PGE(2) concentration (P <or= 0.01) were obtained in group C horses in response to LPS concentrations of 1.0 microg/mL (and higher) after exposure for 24, 36 and 48 h, whereas explants from group A h...
In vivo administration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate. The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) record...
Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses. The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same sur...
Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing. The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. Body fluid drug concentrations were determined by the use of high performance liquid chromatography (HPLC). On day 7, mean voriconazole concentrations of plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, epithelial lining fluid (ELF), and urine were 1.47 +/- 0.63, 0.61 +/- 0.22, 0.70 +/- 0.20, 0.62 +/- 0.26, 0.55 +/- 0.32, 79.45 +/- 69.4, and 1.83 +/- 0.44 microg...
Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses. Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/m...
Characterization of bradykinin-induced endothelium-independent contraction in equine basilar artery. We investigated the effect of bradykinin (BK) on isolated equine basilar arterial rings with and without endothelium. BK induced concentration-dependent contraction of resting arterial rings and no relaxation when the rings were precontracted by prostaglandin F(2alpha). The maximal response and pD(2) value were 161.2 +/- 28.1% (to 60 mm KCl-induced contraction) and 8.24 +/- 0.25 respectively. The cumulative concentration-response curve for BK was not shifted to the right by des-Arg(9)-[Leu(8)]-BK (a B(1)-receptor antagonist), HOE140 (a B(2)-receptor antagonist) or NPC567 (another B(2)-receptor...
Multiple oral dosing of valacyclovir in horses and ponies. The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF wer...
Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky. Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injure...
Effects of dobutamine on cardiac index and arterial blood pressure in isoflurane-anaesthetized horses under clinical conditions. Volatile agent-induced hypotension may contribute to anaesthetic-related morbidity and mortality in horses. Dobutamine is commonly used to support arterial blood pressure (ABP) but little is known about its cardiovascular effects under clinical conditions. The aim of this clinical study was to elucidate the relationship between cardiovascular function and dobutamine infusion in isoflurane-anaesthetized horses. Forty-four horses anaesthetized for a variety of surgical procedures were studied. Premedication with acepromazine, methadone and detomidine was followed by induction of anaesthesia with...
Synthesis and detection of toltrazuril sulfone and its pharmacokinetics in horses following administration in dimethylsulfoxide. Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of abs...
Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals. The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six...
Effects of dermal dexamethasone application on ACTH and both basal and ACTH-stimulated cortisol concentration in normal horses. There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH-stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone-containing dermal ointment is necessary to dete...
P-glycoprotein in intestines, liver, kidney and lymphocytes in horse. P-glycoprotein (P-gp) is an important drug transporter, which is expressed in a variety of cells, such as the intestinal enterocytes, the hepatocytes, the renal tubular cells and the intestinal and peripheral blood lymphocytes. We have studied the localization and the gene and protein expression of P-gp in these cells in horse. In addition we have compared the protein sequence of P-gp in horse with the protein sequences of P-gp in several other species. Real time RT-PCR and Western blot showed gene and protein expression of horse P-gp in all parts of the intestines, but there was no strict cor...
Detection and pharmacokinetics of tetrahydrogestrinone in horses. The anti-doping rules of national and international sport federations ban any use of tetrahydrogestrinone (THG) in human as well as in horse sports. Initiated by the THG doping scandals in human sports a method for the detection of 3-keto-4,9,11-triene steroids in horse blood and urine was developed. The method comprises the isolation of the analytes by a combination of solid phase and liquid-liquid extraction after hydrolysis and solvolysis of the steroid conjugates. The concentrations of THG in blood and urine samples were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
Regulation of platelet activating factor-induced equine platelet activation by intracellular kinases. Lipopolysaccharide (LPS) can activate equine platelets directly or indirectly, via leukocyte-derived platelet activating factor (PAF). Thromboxane (Tx) production by LPS-stimulated equine platelets requires p38 MAPK and this kinase has been suggested as a therapeutic target in endotoxaemia. The present study has utilised selective inhibitors to investigate the role of p38 MAPK and two other kinases, phosphatidylinositol-3 kinase (PI3K) and protein kinase C (PKC), in regulating PAF-induced Tx production, aggregation and 5-HT release in equine platelets, and the modification of these responses b...
The formation of aminorex in racehorses following levamisole administration. A quantitative and chiral analysis following synthetic aminorex or levamisole administration vs. aminorex-positive samples from the field: a preliminary report. Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole. This study examines the urine concentrations of aminorex as a function of time following administration of synthetic, racemic aminorex. Confirmation of the presence of aminorex in urine samples from the horses known to be treated with levamisole is also presented as are data concerning the concentrat...
Pharmacokinetics of butorphanol in horses after intramuscular injection. A two-way cross-over study of the pharmacokinetics of butorphanol after intravenous and intramuscular administration at 0.08 mg/kg in six adult horses was performed. Heparinized venous blood samples were obtained prior to drug administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV injection. Samples were obtained at the same time points and at 6 h and 12 h after IM injection. Physical examination parameters were recorded at each time point. Plasma butorphanol concentrations were determined by high performance liquid chromatography. No significant differences in any physi...
Pyrilamine in the horse: detection and pharmacokinetics of pyrilamine and its major urinary metabolite O-desmethylpyrilamine. Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations p...
Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses. In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-i...
Stereoselective biotransformation of ketamine in equine liver and lung microsomes. Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and,...
Liposome-based diclofenac for the treatment of inflammation in an acute synovitis model in horses. Lameness as a result of joint disease is a major source of decreased athletic performance in the horse. Most treatment protocols include the administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Phenylbutazone, alone or in combination with other treatments, is the most commonly and widely used NSAID, however it has the potential for serious side effects. The introduction of the liposome-based formulation of the NSAID diclofenac has shown promising effect as a safe and convenient treatment for lameness associated with osteoarthritis. The purpose of this study was to evaluate the effe...
Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administration. The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were...
Drug contamination of the equine racetrack environment: a preliminary examination. Advances in analytical technology now make it feasible to detect and confirm exceptionally low concentrations (pg to fg/mL) of drugs and their metabolites in equine biological fluids. These new capabilities complicate the regulatory interpretation of drug positives and bring into question the fair application of medication rules. Such approaches and policies are further complicated by the possibility that drug positives may arise from contamination of the equine environment on the backstretch of the race track. This manuscript provides data demonstrating that the general environment of the bac...
Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves. Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroS...