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 |
Clinical efficacy of local administration of ceftiofur in a Staphylococcus aureus infection in tissue cages in ponies. Ceftiofur concentrations in an infected and uninfected environment were compared and the efficacy of locally administered ceftiofur was evaluated in an experimental infection with Staphylococcus aureus in tissue cages. Eight ponies had tissue cages (TCs) implanted s.c. on each side of the neck. Into one of the cages 150 mg of ceftiofur was administered and fluid samples were taken to determine ceftiofur concentrations. After 1 week the other TC was infected with S. aureus and subsequently treated with 150 mg ceftiofur administered locally into the TC once daily for 21 days. Samples of fluid we...
Pharmacological characterization of alpha1-adrenoceptors in equine digital veins. Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been implicated in a number of conditions, such as acute equine laminitis, and are therapeutic targets for the treatment of this condition. Digital veins, rather than arteries, were investigated in the present study because they have been specifically implicated in the pathophysiology of acute laminitis. The order of potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists was determined in isolated rings of EDVs under ...
Regional differences in the in vitro penetration of hydrocortisone through equine skin. Little is known about the transdermal penetration of hydrocortisone in the horse and, although commercial formulations containing hydrocortisone are registered for topical use in the horse, there have been no studies investigating the movement of this glucocorticoid through different regions of equine skin. Skin was harvested from the thorax, groin and leg (dorsal metacarpal) regions of five Thoroughbred geldings and frozen (-20 degrees C) until required. Defrosted skin was placed in Franz-type diffusion cells and the amount of radiolabelled ((3)H) hydrocortisone, in a saturated solution of un...
In vitro effects of bethanechol on equine gastrointestinal contractility and functional characterization of involved muscarinic receptor subtypes. The goal of this study was to investigate the effect of bethanechol (BeCh) on contractility patterns of smooth muscle preparations of equine duodenum descendens, jejunum, caecum and pelvic flexure in vitro. Concentration-response relationships were developed for BeCh using in vitro assays with and without preincubation of muscarinic (M) receptor antagonists for M2 and M3 receptors. BeCh induced a significant, concentration-dependent increase in contractile response in equine intestine in specimens with circular orientation. The maximal effect was largest for jejunal specimens with no differenc...
Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration. The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume o...
Pharmacokinetics of imipenem-cilastatin following intravenous administration in healthy adult horses. In two studies, six healthy adult horses were given imipenem-cilastatin by slow intravenous (i.v.) infusion at an imipenem dosage of 10 mg/kg (study 1) and 20 mg/kg (study 2). The same horses were used in each dosage schedule, with a 2-week washout period between studies. In each dosage group, serial blood and synovial fluid samples were collected for 6 h after completion of the infusion. HPLC was used to determine the imipenem concentration in all samples. Imipenem was well tolerated by all horses at both dosages; no adverse effects were noted during the study period or during the 24-hour pos...
L-Bupivacaine 0.5% vs. racemic 0.5% bupivacaine for caudal epidural analgesia in horses. Bupivacaine is available as a racemic mixture of its enantiomers, d-bupivacaine and l-bupivacaine (LB). The aim of this randomized, double-blind study was to investigate the clinical efficacy and safety of S(-)-bupivacaine compared with standard racemic bupivacaine (RB) in horses under caudal epidural analgesia. Two treatments were administered to each horse, with a 2-week interval between subsequent treatments. Treatment 1 consisted of 0.5% LB at a dose of 0.06 mg/kg of body weight, and treatment 2 consisted of 0.5% RB at a dose of 0.06 mg/kg of body weight. Epidural injections were given in ...
Comparison of topical lidocaine/prilocaine anesthetic cream and local infiltration of 2% lidocaine for episioplasty in mares. Local anesthesia and tissue inflammation associated with lidocaine infiltration and lidocaine/prilocaine topical anesthetic cream for episioplasty in mares were compared. Twenty-two mares were randomly assigned to lidocaine or lidocaine/prilocaine topical anesthetic cream treatment groups. Perineum and vulva were cleaned, 8-12 g (approximately 1 g/cm per side of vulva) of topical anesthetic cream was applied, and the area was covered by plastic wrap 30 min prior to beginning procedure. Alternately, lidocaine was injected (1 mL) every centimeter just prior to the procedure. Episioplasty was con...
Pharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of the effect of dexamethasone on endogenous hydrocortisone and cortisone in the horse. A compartmental model was used to describe the pharmacokinetics of dexamethasone (DXM) and changes in the plasma concentration of endogenous cortisone (COR) and hydrocortisone (HYD) following intravenous (i.v.) administration of DXM (0.05 mg/kg) in horses. Quantification of DXM, COR and HYD in equine plasma was achieved using liquid chromatography interfaced with triple spray quadrupole quantum tandem mass spectrometry (LC/TSQ-MS/MS). The median alpha (t(1/2alpha)), beta (t(1/2beta)), and gamma (t(1/2gamma)) half-lives were 0.33, 2.2, and 10.7 h respectively. The area under the DXM plasma conc...
Clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine in a Streptococcus equi subsp. zooepidemicus infection model in ponies. Tissue chambers, implanted subcutaneously in the neck in six ponies, were inoculated with Streptococcus equi subsp. zooepidemicus in order to determine the clinical efficacy of prophylactic administration of trimethoprim/sulfadiazine (TMP/SDZ) against this infection. The TMP/SDZ treatment consisted of one intravenous (i.v.) injection of 5 mg/kg TMP and 25 mg/kg SDZ and the same dose of TMP/SDZ per os (p.o.), both given 3 h before inoculation. The oral dose was then repeated every 12 h for 5 days. TMP/SDZ concentrations in tissue chamber fluid (TCF) were above 10 times MIC at the moment of inoc...
Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion. Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-)...
Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administ...
Population pharmacokinetics of marbofloxacin in horses: preliminary analysis. Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance ...
Cefotaxime kinetics in plasma and synovial fluid following intravenous administration in horses. Cefotaxime powder was diluted with sterile water to a concentration of 100 mg/mL. The volume of solution was adjusted for each experimental horse to provide a total dose of 15, 20, and 25 mg/kg and was administered by infusion through a jugular vein catheter over a 10-min period. All three doses were administered to each of the six experimental horses at three different times. Cefotaxime concentrations in plasma and synovial fluid samples were measured by high-performance liquid chromatography (HPLC). Standard compartmental analysis techniques and the WinSAAM modeling program were used to dete...
Disposition of flunixin meglumine injectable preparation administered orally to healthy horses. An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Tissue distribution of clenbuterol in the horse. Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)...
Pharmacokinetics and disposition of clenbuterol in the horse. The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life (t(1/2k)) of 9.2 h, area under the time-concentration curve (AUC) of 12.4 ng.h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution (V(d)) was 1616.0 mL/kg and plasma clearance (Cl) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrati...
Intramuscular dosing strategy for ampicillin sodium in horses, based on its distribution into tissue chambers before and after induction of inflammation. The Pharmacokinetics (PK) and distribution into tissue chamber fluid (TCF) of intramuscularly (i.m.) administered ampicillin sodium were examined in horses in order to design adequate dosing strategies. Concentration-time curves of ampicillin in plasma and TCF were determined in six horses following administration of 15 mg/kg ampicillin sodium, before and after the induction of local inflammation with 0.5% carrageenan. The calculated parameters were used to simulate various dosage-dosing interval combinations. Ampicillin was absorbed very rapidly following i.m. administration. Plasma concentra...
Detection and quantification of cocaine metabolites in urine samples from horses administered cocaine. Cocaine is a naturally occurring alkaloid that is commonly abused by human-beings for its psychostimulatory effects. Occasionally, very small concentrations (i.e. <100 ng/mL) of the primary cocaine metabolite, benzoylecgonine (BZE) have been detected in urine collected from horses competing in athletic events. In this study urine samples, collected from four horses following the administration of 2.5 and 20 mg of cocaine sublingually and 50 mg of cocaine intravenously, were analyzed for the presence of cocaine and/or its metabolites by enzyme-linked immunosorbent assay (ELISA) and gas chrom...
Characterisation of the response of equine digital arteries and veins to substance P. Substance P (SP), a potent vasodilator, has been detected in equine digital sensory-motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre-constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium- and concentration-dependent manner to SP. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; 300 microm) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely...
Effect of alkalinization on the local analgesic efficacy of ketamine in the abaxial sesamoid nerve block in horses. The objective of this study was to determine the effects of the alkalinization on the local analgesic efficacy of 1% ketamine in the abaxial sesamoid nerve block in horses. Thirty-six mature healthy horses were randomly assigned to four groups for the following treatments; an abaxial sesamoid block with 5 mL of saline solution (control saline); an abaxial sesamoid block with 5 mL of a solution containing 1% ketamine (KETs 1%); an abaxial sesamoid block with 5 mL of a solution containing saline solution and 0.5 mEq of sodium bicarbonate (control bicarbonate); and an abaxial sesamoid block with ...
Clinical efficacy of trimethoprim/sulfadiazine and procaine penicillin G in a Streptococcus equi subsp. zooepidemicus infection model in ponies. Tissue chambers, implanted subcutaneously on both sides of the neck in eight ponies, were inoculated with Streptococcus equi subsp. zooepidemicus in order to compare the clinical efficacy of trimethoprim/sulfadiazine (TMP/SDZ) and penicillin G treatment in a purulent infection. The TMP/SDZ treatment consisted of one intravenous (i.v.) injection of 5 mg/kg TMP and 25 mg/kg SDZ and the same dose of TMP/SDZ per os (p.o.), both given 20 h after inoculation. The oral dose was then repeated every 12 h for 21 days. The penicillin treatment consisted of one i.v. injection of 20 000 IU/kg sodium penici...
In vitro and ex vivo effects of the phosphodiesterase 4 inhibitor, rolipram, on thromboxane production in equine blood. Phosphodiesterase 4 (PDE4) inhibitors have been shown to inhibit equine neutrophil function in vitro and may be of benefit in recurrent airway obstruction (RAO), an allergy-based respiratory disease characterized by inflammatory cell recruitment and activation within the lungs following exposure of susceptible horses to allergens in mouldy hay. The aim of this study was to evaluate the inhibitory effects of the PDE4 inhibitor, rolipram, in an in vitro assay of thromboxane (Tx) production. The assay was then used to monitor the activity of this compound in vivo in normal and RAO-affected horses...
Substance P induces activation, adherence and migration of equine eosinophils. The tachykinin, substance P (SP), affects eosinophil function by direct and indirect mechanisms and has been shown to cause equine eosinophils to adhere to vascular endothelium and to release cytokines that increase cell adherence. The aim of this study was to determine whether SP could act directly on equine eosinophils in vitro. Eosinophil activation was also compared in cells from normal ponies and those with insect hypersensitivity as SP may be released in the skin of hypersensitive animals. SP caused equine eosinophils to adhere, migrate and produce superoxide, although high concentration...
Effects of midazolam and sarmazenil on the equine electroencephalogram during anaesthesia with halothane in oxygen. The electroencephalographic (EEG) effects of a rapid infusion of midazolam and sarmazenil following a bolus of midazolam were investigated in eight Welsh mountain ponies anaesthetized with 0.8% halothane in oxygen. The peak plasma concentration of midazolam was 2.13 +/- 0.34 ng/mL (mean +/- SD) occurring 5 min after the start of the infusion. Sarmazenil concentrations were not measured. The 95% spectral edge frequency of the EEG decreased by a maximum of 39.8 +/- 15.8%, 10 min after the start of the midazolam infusion. No changes were seen in median frequency of the EEG or the second different...
Pharmacokinetics and pharmacodynamics of clemastine in healthy horses. Clemastine is an H1 antagonist used in certain allergic disorders in humans and tentatively also in horses, although the pharmacology of the drug in this species has not yet been investigated. In the present study we determined basic pharmacokinetic parameters and compared the effect of the drug measured as inhibition of histamine-induced cutaneous wheal formation in six horses. The most prominent feature of drug disposition after intravenous dose of 50 microg/kg bw was a very rapid initial decline in plasma concentration, followed by a terminal phase with a half-life of 5.4 h. The volume of d...