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0000-0002-4182-903X
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James Cook University
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Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1751-0813.1996.TB10008.X
Abstract: Enzyme immunoassay for prostaglandin E2 (PGE2), and radioimmunoassays for prostaglandin F2 alpha (PGF2 alpha), 6-keto-PGF1 alpha, and leukotriene B4 (LTB4) were performed on synovial fluid from normal middle carpal joints of 10 horses, and from 30 middle carpal or antebrachiocarpal joints of horses affected by degenerative joint disease and chip fractures to compare the concentrations of inflammatory mediators. Significantly greater concentrations of PGE2 were detected in fluid from affected than from control joints, but there were no significant differences in the mean concentrations of PGF2 alpha, 6-keto-PGF1 alpha, and LTB4.
Publisher: Wiley
Date: 04-08-2000
Publisher: Informa UK Limited
Date: 08-1996
DOI: 10.1080/00480169.1996.35958
Abstract: Two commercial formulations of cephalexin were administered intramuscularly to five heifers and five bulls in a balanced crossover design. Statistically significant and clinically important differences were detected between the two formulations of cephalexin. These results suggest that 24 h dose intervals would be appropriate with only one of the formulations and that the recommended dose rates for each product may need to be reviewed.
Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1365-2885.1996.TB00020.X
Abstract: This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a cross-over using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (i.v.) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin i.v. Plasma s les were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected (P 20%, control values, elimination half-life (t1/2), apparent volume of distribution (Vd), area under the plasma concentration versus time curve (AUC) and mean residence time (MRT) were not altered. For control animals the elimination rate constant (k(el)) and total body clearance (Cl) were 1.35 +/- 0.43 h-1 and 20.2 +/- 6.1 ml/h.kg respectively (mean +/- SD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.
Publisher: Wiley
Date: 23-08-2012
DOI: 10.1111/J.1751-0813.2012.00983.X
Abstract: To assess the clinical suitability of alfaxalone as an anaesthetic induction and maintenance agent for kittens aged less than 12 weeks. The study group comprised 34 kittens aged less than 12 weeks that were presented for surgical desexing. They were aged by dentition, examined and weighed prior to premedication with acepromazine, atropine and morphine. At 20-30 min after premedication, animals were anaesthetised with intravenous alfaxalone administered to effect, using a target maximum expected dose of 5 mg/kg. All cats were intubated: 25 were maintained with isoflurane in oxygen administered with a non-rebreathing circuit and 8 were maintained by supplemental intravenous administration of alfaxalone. Subjective measures of anaesthetic quality and vital signs were recorded from enrolment to recovery. Cats receiving supplemental alfaxalone for maintenance were evaluated for time to first supplemental dose and the total dose of supplemental alfaxalone (mg/kg/h). Descriptive and comparative statistics were used to analyse and present collected data. The mean (± SD) dose of alfaxalone for induction was 4.7 ± 0.5 mg/kg body weight. Subjective measures of anaesthetic quality indicated acceptable induction, maintenance and recovery standards. Measured cardiovascular and respiratory parameters were well maintained. Alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (Alfaxan®) is a suitable injectable anaesthetic induction agent for juvenile cats aged less than 12 weeks requiring anaesthesia. Maintenance of anaesthesia with supplemental doses of alfaxalone may be a suitable alternative in kittens when the use of inhalant anaesthetic maintenance is not feasible.
Publisher: Wiley
Date: 10-09-2009
Publisher: Elsevier BV
Date: 06-2013
Publisher: Wiley
Date: 11-1999
Publisher: Wiley
Date: 12-1996
DOI: 10.1111/J.1365-2885.1996.TB00082.X
Abstract: This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone concentration determination by high-performance liquid chromatography. All gentamicin data were best approximated by a two-compartment open model using sequential, weighted non-linear regression. Pharmacokinetic parameters were calculated using model-dependent formulae. Phenylbutazone data were analysed by non-compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment from peripheral tissues (k21) (P < 0.05) and there was a trend to a 24% increase in k12 (P = 0.052). The gentamicin elimination half-life was decreased 23% and the Vd(urea) was reduced by 26%. No induction by gentamicin of changes in phenylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of distribution and elimination of gentamicin. Therefore, care should be exercised in the use of aminoglycosides in equine patients concurrently maintained on phenylbutazone.
Publisher: Wiley
Date: 06-1998
DOI: 10.1111/J.1751-0813.1998.TB12396.X
Abstract: In Saudi Arabia, the epidemiology of rheumatoid arthritis (RA) is not well studied and is marked by inconsistencies in clinical diagnosis. Therefore, in this study, we explored the prevalence, clinical characteristics, and diagnostic validity of a prediction score based upon disease markers in orthropedic clinics' patients in the Madinah region of Saudi Arabia. The clinical data for this retrospective cross-sectional study were retrieved from the database registry of orthopedic clinics in selected hospitals of the Medinah province of Saudi Arabia. Sociodemographic features, disease markers and the clinical characteristics were collected for a period of 6 months, from December 1, 2020, to May 31, 2021. The prediction score was generated from the sum of disease markers, coded as dichotomous variables. The total s le size of our study was 401. The prevalence of RA in the study subjects ( There was a moderately high prevalence of RA in patients visiting the orthropedic clinics of the selected hospitals of Madinah region of Saudi Arabia. The diagnostic validity of the prediction score, though promising, was slightly lower than the acceptable range.
Publisher: Wiley
Date: 1999
DOI: 10.1111/J.1740-8261.1999.TB01831.X
Abstract: Reference ranges for gastric emptying time (GET), small intestinal transit time (SITT), and colonic transit time of 1.5-mm and 5-mm radiopaque markers in healthy cats fed a high-fiber meal were determined, and the influence of low-dose diazepam intravenous injection on the gastrointestinal transit of the markers was examined. The mean GETs and SITTs, and the mean residence times (MRTs) and geometric centers (GCs) of markers in the colon were determined. The effect of intravenous diazepam injection and marker size on these parameters was examined. Diazepam injection had no significant influence on gastrointestinal transit. The GETs of the 1.5-mm markers were significantly more rapid than those of the 5.0-mm markers. There were no significant differences between the SITTs or GCs of the 1.5-mm and 5.0-mm markers. Reference values were developed for GET, SITT, and colonic transit of radiopaque markers for cats fed a high-fiber meal. Diazepam injection had no effect on these parameters.
Publisher: American Dairy Science Association
Date: 11-2020
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1111/J.1467-2995.2005.00264.X
Abstract: To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU). Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood s les were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD. The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed. Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.RVSC.2011.10.003
Abstract: Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1×, 2×, 5×, 10× and 20× multiples of the labelled doses (2mg/kg for alfaxalone 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1×) doses of each drug but became apnoeic at 5× dose of propofol versus 20× dose of alfaxalone. For propofol at 2× and 5× doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2×, 5× and 10× doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5×) than for propofol (2×) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone.
Publisher: Informa UK Limited
Date: 12-1997
DOI: 10.1080/00480169.1997.36034
Abstract: Combination formulations of penicillin G salts and dihydrostreptomycin were developed during the 1960s and are currently marketed in New Zealand for parenteral and intramammary use in dairy cattle. In this paper, the second part of a two paper series, the mechanisms by which bacteria develop resistance to each of these drugs independently is reviewed and the impact of this resistance on potential for synergy is discussed. Further, the considerable potential for tissue drug residues with dihydrostreptomycin or streptomycin from these formulations is examined by re-analysis of literature data, demonstrating an urgent need to reassess the place for aminoglycoside-containing formulations in dairy cattle therapeutics.
Publisher: Wiley
Date: 21-01-2019
DOI: 10.1111/JVP.12740
Abstract: Alfaxalone, a synthetic neuroactive steroid, has been attributed with properties including sedation, anaesthesia and analgesia. The clinical relevance of any analgesic properties of alfaxalone has not been demonstrated. This study was a prospective, blinded, randomized, negative control clinical trial in 65 healthy dogs presented for ovariohysterectomy. Anaesthesia was induced and maintained, for Group 1 (TIVA) dogs (n = 30) with intravenous alfaxalone alone and for Group 2 dogs (n = 35) with thiopental followed by isoflurane in 100% oxygen inhalation. After ovariohysterectomy, quantitative measures of pain or nociception were recorded at 15 min intervals for 4 hr using three independent scoring systems, a composite measure pain scale (CMPS), von Frey threshold testing and measures of fentanyl rescue analgesia. The mean CMPS scores of Group 2 (THIO/ISO) dogs remained higher than Group 1 (TIVA) dogs from 15 to 135 min post-surgery but this difference was not statistically significant. There were no significant differences between groups in the proportions of dogs requiring rescue fentanyl analgesia, the total fentanyl dose used or the time to first fentanyl dose. The Von Frey threshold testing was found to be unsuitable for measurement of pain in this experimental model. When administered as total intravenous anaesthesia, alfaxalone did not provide analgesia in the postoperative period.
Publisher: Wiley
Date: 02-2013
DOI: 10.1111/EVJ.12000
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.RVSC.2013.01.003
Abstract: Pro-inflammatory cytokines, such as IL-1β and TNFα, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. β2 agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNFα, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration of low dose endotoxin (30 ng/kg over 30 min). Clinical signs were measured and leukocyte counts and serial blood s les were obtained over 6 h. Pre-treatment with oral clenbuterol (0.8 μg/kg) significantly reduced (P=0.046) the peak rectal temperature and the peak plasma TNFα concentration (P=0.026) following endotoxin challenge. These data suggest that oral clenbuterol at the therapeutic dose has anti-inflammatory effects in horses challenged with a low dose of endotoxin.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1111/J.1467-2995.2008.00406.X
Abstract: To determine the cardiorespiratory and anesthetic effects of 2, 6, and 20 mg kg(-1) IV alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan) in dogs. Blinded four-way crossover randomized by dose. Eight healthy adult purpose-bred mixed breed dogs (four male, four female) weighing between 12 and 28 kg. Four (0, 2, 6, 20 mg kg(-1)) IV treatments of alfaxalone were administered to each dog with a 3-hour washout period between doses. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH, blood gases (PaO(2), PaCO(2)) were performed prior to and at predetermined intervals after drug administration. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia were categorically scored as was the response to noxious stimulation. The administration of alfaxalone resulted in dose-dependent changes in cardiovascular and respiratory parameters. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses with most variables returning to baseline in 15-30 minutes. Respiratory rate, minute volume, and PaO(2) decreased and apnea was the most common side effect. The duration of anesthesia increased with dose, and induction, maintenance, and recovery were judged to be good to excellent with all doses studied. Alfaxalone produced good to excellent short-term anesthesia in unpremedicated dogs. Cardiorespiratory effects were minimal at lower doses. Anesthesia was judged to be good to excellent and associated with unresponsiveness to noxious stimulation for the majority of anesthesia. Hypoventilation and apnea were the most prominent and dose-dependent effects.
Publisher: Elsevier BV
Date: 2009
DOI: 10.1111/J.1467-2995.2008.00428.X
Abstract: To determine the cardiorespiratory and anesthetic effects of 0, 5, 15, and 50 mg kg(-1) intravenous (IV) alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan Jurox Pty Ltd, Rutherford, NSW, Australia) in cats. Four treatments of alfaxalone were administered in sequential order. Eight healthy adult cats (four male four female) weighing between 3.71 and 5.91 kg. Cats were instrumented for hemodynamic measurements. Four (0, 5, 15, and 50 mg kg(-1)) IV doses of alfaxalone were administered over one minute, with a 3-hour washout period between doses 0, 5, and 15 mg kg(-1) on Day 0. The 50 mg kg(-1) treatment was administered 24 hours later. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH and blood gases (PaO(2), PaCO(2)) were performed at pre-determined intervals. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia and the response to noxious stimulation were categorically scored. Alfaxalone administration resulted in dose-dependent cardiorespiratory depression. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses. Most variables returned to baseline by 15-30 minutes. Respiratory rate, minute volume, and PaO(2) decreased. Apnea was the most common side effect. Induction and maintenance quality were judged to be good to excellent at all doses and quality of recovery good to excellent at all but the 50 mg kg(-1) dose. The duration of anesthesia and unresponsiveness to noxious stimulation increased with dose. The administration of the 50 mg kg(-1) dose produced marked cardiorespiratory depression and apnea. Alfaxalone produced dose-dependent anesthesia, cardiorespiratory depression and unresponsiveness to noxious stimulation in unpremedicated cats. Hypoventilation and apnea were the most common side effects.
Publisher: Wiley
Date: 04-1995
DOI: 10.1111/J.1365-2885.1995.TB00565.X
Abstract: Plasma (P), synovial fluid (SF) and lymph (L) concentrations of gentamicin were studied in two trials. A lymph vessel in the hindlimb was cannulated. The day after surgery (trial A), P and L s les were collected for 12 h after intravenous injection of gentamicin sulphate at 2.2 mg/kg dose rate. Approximately 48 h after surgery (trial B), the fetlock joint of the cannulated hindlimb was catheterized and P, SF and L s les collected for 12 h after a similar intravenous injection. The kinetic parameters were similar to those in other reports and did not differ between trials (P < 0.05). The P, L and SF disposition profiles were similar. The 95% confidence interval for P & L concentrations overlapped 2-3 h after injection. Thereafter, parallelism between L and P concentrations was observed, but L concentrations were on average 60% higher than P concentrations, and elimination from L was slower than from P. The mean L/SF and P/SF ratios were 1.54 +/- 0.2 and 1.25 +/- 0.2, 2-4 h after injection. Gentamicin elimination from SF appeared to be slower than from L and P. Lymph cannulation is a viable technique for antibiotic disposition studies. A s le of any of the fluids 3 h after injection was representative of the others. While SF concentrations were of limited value for predicting tissue fluid (L) concentrations 3-8 after injection, P concentrations were a useful index.
Publisher: Wiley
Date: 23-08-2017
DOI: 10.1002/DTA.2236
Abstract: The doping of greyhound dogs with testosterone is done in an attempt to improve their athletic performance, but such doping cannot easily be confirmed, especially in male dogs owing to the natural presence of endogenous testosterone. As testosterone is usually administered as its esters, their direct detection in hair would provide confirmatory evidence of the administration of a pharmaceutical product. This article demonstrates that the use of a liquid chromatography-high resolution mass spectrometry method with heated electrospray ionisation (HESI) combined with the use of amino solid-phase extraction (SPE) cartridges for s le clean-up, is suitable for the sensitive determination of propionate, phenyl propionate, isocaproate, decanoate, and enanthate esters of testosterone in greyhound hair. The method is linear over the range, 0.1 μg/kg-10 μg/kg, for all the testosterone esters analysed. The limits of detection (LOD) are 0.05 μg/kg for testosterone phenyl propionate, isocaproate, and decanoate, 0.025 μg/kg for testosterone propionate, and 0.25 μg/kg for testosterone enanthate. This method was applied to hair s les collected from male greyhounds before and after a single administration of a product containing several testosterone esters, each of which could be detected up to 100 days post-administration. The study also demonstrates that tail hair is the specimen of choice for the analysis of testosterone in dog hair and that washing of dogs does not impact the analysis of testosterone esters in hair. This method may be useful in racing regulation for the detection of illegitimate use of testosterone in all species.
Publisher: Wiley
Date: 24-07-2012
DOI: 10.1111/J.1751-0813.2012.00974.X
Abstract: To assess the efficacy of alfaxalone as an anaesthetic induction agent for dogs aged less than 12 weeks. The study group comprised 25 juvenile dogs aged less than 12 weeks that were presented for surgical desexing. Dogs were aged by dentition, examined and weighed prior to premedication with acepromazine, atropine and morphine. At 20-30 min after premedication, animals were anaesthetised with intravenous alfaxalone administered to effect, using a target maximum expected dose of 2 mg/kg. Dogs were intubated and anaesthesia was maintained with isoflurane in oxygen administered with a non-rebreathing system. Subjective measures of anaesthetic quality and vital signs were recorded from enrollment to recovery. Descriptive and comparative statistics were used to analyse and present collected data. The mean (± SD) dose of alfaxalone for induction was 1.7 (± 0.3) mg/kg body weight. Subjective measures of anaesthetic quality indicated acceptable induction, maintenance and recovery standards. Measured cardiovascular and respiratory parameters were well maintained. Alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (Alfaxan®) is a suitable injectable anaesthetic induction agent for dogs aged less than 12 weeks requiring anaesthesia.
Publisher: American Veterinary Medical Association (AVMA)
Date: 07-2002
Abstract: Objectives —To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo. Animals —8 adult ponies. Procedure —Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO 3 – were exposed to PBZ, bumetanide, or indomethacin. Bidirectional Cl – fluxes were determined. After a baseline flux period, prostaglandin E 2 (PGE 2 ) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed. Results —Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE 2 . After PGE 2 was added, Cl – secretion increased significantly in tissues in HCO 3 - – -free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE 2 . Bumetanide did not affect baseline short circuit current and Cl – fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin. Conclusions and Clinical Relevance —Prostaglandin- induced Cl – secretion appeared to involve a transporter that might also secrete HCO 3 – . Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl – and HCO 3 – secretion. ( Am J Vet Res 2002 :934–941)
Publisher: Wiley
Date: 11-11-2008
DOI: 10.1111/J.1365-2885.2008.00998.X
Abstract: This study aimed to determine the pharmacokinetic parameters and pharmacodynamics of alfaxalone in a 2-hydroxypropyl-beta-cyclodextrin alfaxalone formulation (Alfaxan), Jurox Pty Ltd, Rutherford, NSW, Australia) in cats after single administration at clinical and supraclinical dose rates and as multiple maintenance doses. First, a prospective two-period cross-over study was conducted at single clinical and supraclinical doses. Second, a single group multiple dose study evaluated the effect of maintenance doses. Eight (five female and three male) domestic cats completed the cross-over experiment and six female cats completed the multiple dose study. In the first experiment, alfaxalone was administered intravenously (IV) at 5 or 25 mg/kg with a washout period of 14 days. In the second experiment, alfaxalone was administered IV at 5 mg/kg followed by four doses each of 2 mg/kg, administered at onset of responsiveness to a noxious stimulus. Blood was collected at prescribed intervals and analysed by LCMS for plasma alfaxalone concentration. Noncompartmental pharmacokinetics were used to analyse the plasma alfaxalone data. The plasma clearance of alfaxalone at 5 and 25 mg/kg differed statistically at 25.1 and 14.8 mL/kg/min respectively. The elimination half lives were 45.2 and 76.6 min respectively. Alfaxalone has nonlinear pharmacokinetics in the cat. Nevertheless, for cats dosed with sequential maintenance doses, a regression line through their peak plasma concentrations indicated that there was no clinically relevant pharmacokinetic accumulation. The duration of nonresponsiveness after each maintenance dose was similar at approximately 6 min, indicating a lack of accumulation of pharmacodynamic effect. The cardiovascular and respiratory parameters measured in cats after administration of the labelled doses of Alfaxan were stable. In conclusion, the pharmacokinetics of alfaxalone in cats are nonlinear. At clinical dose rates, however, neither alfaxalone nor its effects accumulated to a clinically relevant extent. Further, in the un-premedicated cat the induction and maintenance of surgical anaesthesia was free of untoward events after a dose of 5 mg alfaxalone/kg body weight followed by four sequential doses of 2 mg/kg as needed (i.e., approximately 7 to 8 mg/kg/h).
Publisher: Wiley
Date: 04-07-2019
DOI: 10.1111/JVP.12778
Publisher: Informa UK Limited
Date: 10-01-1997
DOI: 10.1080/00480169.1997.36022
Abstract: Combination formulations of penicillin G salts and dihydrostreptomycin were developed during the 1960s and are currently marketed in New Zealand for parenteral and intramammary use in dairy cattle. In this paper, the clinical indications and efficacy, pharmacokinetics and potential for antimicrobial synergy of penicillin and dihydrostreptomycin or streptomycin, when combined, are discussed.
Publisher: Wiley
Date: 13-03-2012
DOI: 10.1111/J.1365-2885.2012.01375.X
Abstract: This article explores the numerous challenges encountered when the goal is to demonstrate bioequivalence (BE) between test and reference intramammary (IMM) products in ruminants. Numerous pathophysiological factors of mastitis and physicochemical properties of IMM formulations are implicated in the difficulties in confirming BE for this dosage form. Advantages and disadvantages of current BE study designs are discussed, and alternative perspectives are outlined. Ongoing and future research increasing our knowledge of the pharmacokinetics and pharmacodynamics of antimicrobial drugs delivered through this route is crucial to better understanding the implications of clinically significant formulation differences in the demonstration of BE and may also help in developing more effective IMM formulations for ruminants.
Publisher: Wiley
Date: 11-2010
DOI: 10.1111/J.2042-3306.2010.00219.X
Abstract: Some methods of lactate (LA) measurement have not been validated appropriately for use in horses. To validate 2 LA analysers (YSI 2300 Stat Plus and TDx Lactic Acid Assay) for use with equine plasma and to compare plasma [LA] determined by the 2 methods. Both instruments were evaluated for linearity, parallelism, recovery and precision using serial dilutions of standard LA solutions and equine plasma and then comparing results with linear regression or paired t tests. Plasma [LA] results were compared in 275 blood s les collected from horses exercising at various intensities using Bland-Altman analysis. Level of significance was P < 0.05. YSI exhibited good linearity for both LA standards and equine plasma (P < 0.05) at 0-30 mmol/l. TDx had good linearity at 0-12 mmol/l (P 12 mmol/l and with equine plasma, linearity was decreased. YSI exhibited good parallelism between LA standards and equine plasma LA measurements throughout the 0-30 mmol/l range (P > 0.05). Parallelism was poor with TDx (P < 0.05). Mean ± s.d. % recovery was 101.7 ± 3.4% for YSI (acceptable) and 110.6 ± 8.4% for TDx (unacceptable). Within-run and mean between-run coefficients of variation (CV) for plasma s les tested from 3.3-29.5 mmol/l were 0.4-3.0% for YSI. CVs for s les tested from 2.8-8.0 mmol/l were 17.4-24.1% for TDx. In 275 plasma s les, [LA] ranged from 0.1-42.7 mmol/l and 0.3-50.6 mmol/l for the YSI and TDx methods, respectively. The difference in plasma [LA] determined by the 2 methods was -1.0 ± 3.2 mmol/l, documenting that the TDx overestimated the YSI results by a mean value of 1 mmol/l. It was concluded that the YSI method was a reliable method for measuring equine plasma [LA] from 0-30 mmol/l. The TDx method was found not to be suitable for use with equine plasma due to greater variability in measurements (high CV).
Publisher: Wiley
Date: 25-09-2019
DOI: 10.1111/JVP.12812
Abstract: Understanding the pharmacokinetics of intra-mammary antibiotics is important for the prediction of drug residues in milk and for the design of optimal dosage regimens. Unfortunately, compartmental pharmacokinetic models are not valid for this unique system. A minimal physiologically based pharmacokinetic model is presented incorporating the physiology of milk secretion, drug administration at the quarter level, drug absorption and dispersion, drug retention during the inter-milking interval and episodic drug elimination at milking. The primary objective of the study was the development and exploration of a model for major factors controlling drug concentration in milk, rather than generation of rigorously predictive pharmaco-statistical models for any particular drug. This model was implemented in a two-stage approach, using published concentration data for penicillin, cefuroxime, cephapirin and desacetyl-cephapirin in milk of healthy cows. Model simulations evaluated sensitivity and developed predictions of drug residues. The model successfully predicted both drug concentrations and drug residues in milk. The postmilking residual milk volume did not adequately explain antibiotic pharmacokinetics, requiring additional considerations for drug retention. Local sensitivity analysis indicated that increasing the number of quarters treated, the dosage, or the duration of the inter-milking interval prolonged both the persistence of drug residues and the duration that antibiotic concentration exceeded typical minimum inhibitory concentrations. The model was flexible across different beta-lactam drugs as a general description of intra-mammary pharmacokinetics. This model is suitable for the design and analysis of dosage regimens, and could be applied for the prediction of withholding periods when these antibiotic preparations are used off-label. The final model indicates that explicit consideration of the milking regimen is fundamental to the design and interpretation of pharmacokinetic studies of antibiotics in bovine milk.
Publisher: Wiley
Date: 09-1993
DOI: 10.1111/J.1751-0813.1993.TB00871.X
Abstract: Six adult ponies were injected in the same intramuscular site with kanamycin sulphate (10 mg/kg). Two hours later, arthrocenteses of the right metacarpophalangeal, radio-carpal, intercarpal, tibio-tarsal and metatarsophalangeal joints were performed within 3 minutes. Arthrocenteses of the same joints on the left side were conducted 5 hours later. When expressed as a percentage of plasma drug concentration, differences in synovial fluid drug concentration between the joints s led at 2 and 5 hours after injection were not detected.
Publisher: Wiley
Date: 12-12-2011
DOI: 10.1111/J.1365-2885.2011.01352.X
Abstract: Antimicrobial drugs are often infused directly through the streak canal into the bovine udder for the treatment or prevention of mastitis. These infusions have two major problems: drug residues in milk and variable antimicrobial efficacy. Both problems are influenced by the pharmacokinetics of intramammary delivery and elimination of drugs. This pharmacokinetics does not conform to the assumptions of traditional first-order mamillary pharmacokinetic models. To help understand drug delivery into and elimination from the udder, a new approach to pharmacokinetic modelling of the udder is proposed. This new model was used to predict the movement of drug within the udder and the concentrations of drug achieved within physiological compartments of the udder. These predictions were examined using computer modelling. The model was evaluated using data from in vivo intramammary infusion of cefuroxime. The model predicts that changes in milking efficiency (residual volume), milk productivity and milking frequency can impact both the drug residue persistence and the time that milk drug concentrations exceed the minimum inhibitory concentrations for pathogens. The model provides a new tool for future evaluation of intramammary dosing studies.
Publisher: Wiley
Date: 14-09-2010
Publisher: Wiley
Date: 12-1995
DOI: 10.1111/J.1365-2885.1995.TB00621.X
Abstract: The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate of proteoglycan synthesis and the number of pyknotic nuclei as a measure of cell death. During culture, control explants remained metabolically active and viable but suffered a net loss of proteoglycans. Proteoglycan loss was reduced by the presence of either phenylbutazone or Depo-Medrol. This effect was significant at clinically relevant concentrations of phenylbutazone (2-20 micrograms/mL), but not Depo-Medrol (20-200 micrograms/mL). Depo-Medrol caused a dose-dependent suppression of proteoglycan synthesis at all concentrations, but chondrocyte viability was affected only at the 2000 micrograms/mL dose. Phenylbutazone affected proteoglycan synthesis and cell viability only at the 2000 micrograms/mL concentration. At all concentrations, the anticatabolic effects of each drug influenced the proteoglycan content of the explants far more than did any antianabolic or cytotoxic drug effect. The results suggest that the therapeutic potential of both phenylbutazone and Depo-Medrol may not be restricted to their anti-inflammatory effects on the soft tissues of the joint.
No related grants have been discovered for Ted Whittem.