Pharmacologie clinique des bisphosphonates : revue de littérature axée sur le tiludronate chez le cheval.

in Annales de Médecine Vétérinaire (2007), 151

Comparative bioavailability of two intravenous dosage rates of tiludronic acid in healthy adult horses

Report (2007)

Comparative pharmacokinetics of two intravenous dosage rates of tiludronate in healthy adult horses

Conference (2007)

Plasma and urine pharmacokinetics of tiludronate administered once daily as an intravenous bolus of 0.1 mg/kg for ten consecutive days (group 1, n=6) was compared to a single slow infusion of 1 mg/kg ... [more ▼]

Plasma and urine pharmacokinetics of tiludronate administered once daily as an intravenous bolus of 0.1 mg/kg for ten consecutive days (group 1, n=6) was compared to a single slow infusion of 1 mg/kg (group 2, n=6) in healthy adult horses. Plasma samples were collected at regular intervals for a period of 16 and 7 days in groups 1 and 2 respectively. Continuous urine collection for determination of cumulative urinary excretion of tiludronate was performed during 16 and 7 days in groups 1 and 2 respectively, and over 24-hour periods every 10 days until 60 days after the last tiludronate administration in both groups. Tiludronate concentrations were obtained in all plasma and urine samples using HPLC with UV detection. Plasma pharmacokinetic parameters were determined using a noncompartmental approach. Group 1 mean (± SD) AUCss was 3.76 (±0.698) mg.h.L-1 and group 2 mean (± SD) AUCtot was 39.07 (±3.699) mg.h.L-1. Mean (± SD) clearance (Cl) was 0.027 (±0.0042) and 0.026 (±0.0022) L.h-1.kg-1 in groups 1 and 2, respectively. Neither the dose corrected AUC (p=0.724) nor the Cl (p=0.528) were statistically different between groups. Relative plasma bioavailability (infusion versus bolus) was 103%. Cumulative urine tiludronic acid excretion could not be compared between groups due to analytical limitations (LOQ of 0.025 mg.L-1), which led to numerous missing data particularly in group 1, and an inability to conduct appropriate statistical and pharmacokinetic analyses. In conclusion, both dosage rates of tiludronate were considered bioequivalent with regards to plasma pharmacokinetics. [less ▲]

History and clinical features of atypical myopathy in horses in Belgium (2000-2005)

in Journal of Veterinary Internal Medicine (2007), 21(6, Nov-Dec), 1380-1391

Background: The emergent nature of atypical myopathy or atypical myoglobinuria (AM) necessitates precise description of its clinical and epidemiologic features. Purpose: To define key features of AM to ... [more ▼]

Background: The emergent nature of atypical myopathy or atypical myoglobinuria (AM) necessitates precise description of its clinical and epidemiologic features. Purpose: To define key features of AM to help practitioners recognize the disease and to advise owners to take preventive measures. Animals: Belgian cases of AM confirmed by histology (CC horses; n = 57) from autumn 2000 to spring 2005 were included in the study. Co-grazing horses (Co-G horses; n = 77) that remained free of any abnormal clinical signs constituted a control croup. Methods: History, environmental characteristics, clinical signs, and laboratory results associated with AM were determined by a retrospective case series study. Results: Young horses in poor or normal body condition were found to be at risk for AM. Pastures were characterized by poor natural drainage and vegetation of low nutritional value. Features of AM were seasonal occurrence, apparent link with weather conditions fie, lack of solar radiation with no heavy frost and an excess of precipitation or relative humidity), sudden onset of clinical signs, and rapid death. Evaluation of serum creatine kinase activity indicated severe muscle destruction in CC horses and subclinical disease in a few Co-G horses. Conclusions: The association of AM with specific environmental conditions and individual animals suggests that young horses should not be pastured on bare premises subject to humidity when the weather has been very wet and cold for several days. Management of AM outbreaks should include control of Co-G horses who are apparently healthy. [less ▲]

Risk factors associated with atypical myopathy in grazing horses

in In Proceedings of the 45th Annual Congress of the British Equine Veterinary Association (2006, September 14)

Assessment of a bone biopsy technique for tiludronic acid dosage in horses: a preliminary study

Poster (2006, September)

Introduction Tiludronic acid as a bisphosphonate has a strong affinity for bone, making difficult the assessment of its PK profile in this deep compartment on living animals. The invasive nature of sample ... [more ▼]

Introduction Tiludronic acid as a bisphosphonate has a strong affinity for bone, making difficult the assessment of its PK profile in this deep compartment on living animals. The invasive nature of sample collection remains a limiting factor. This study was carried out in order to assess a bone biopsy technique allowing the repetition of sampling over a long period of time to dose tiludronic acid in equine bone. Material and Methods Six healthy 4- to 8-year-old Standardbred geldings were treated with tiludronic acid 1 mg/kg in a saline infusion over 30 minutes. The horses were subjected to euthanasia on days 1, 43, 57, 92, 182 and 222 post-treatment, respectively. Bone samples (test samples and larger reference samples) were taken at 4 sites per side and per horse: the lateral aspect of the metacarpal bone III (MCIII) of the forelimb, the 13th rib, the tuber coxae and the cuboïd bone. Test samples were taken with a 5-mm diameter dental drill (Implanteo™, Anthogyr), while larger reference samples were taken around the drill sample sites with an osteotome. All samples were taken immediately after euthanasia. Tiludronic acid concentrations were measured by HPLC with UV detection. Results The tuber coxae was the easiest site to sample. The sample site of the MCIII was easily accessible but due to the extreme hardness of the bone, the drill sampling was technically difficult to perform. Drill samples obtained from the 13th rib were very small, and the access more limited. Finally, the access to the cuboïd bone required considerable dissection, not performable in vivo. Extraction and dosage of tiludronic acid from the MCIII was difficult for technical reasons in most cases, in drill samples as well as in reference samples, and most (96%) of the values obtained were considered unreliable. This was also true for some samples from the 13th rib and from the cuboïd bone, to a lesser extent (42% of unreliable values for both sites). Moreover, for these two sample sites, less technical problems were encountered for the extraction and dosage of tiludronic acid in drill samples than in reference samples. No extraction or dosage problem was encountered with the tuber coxae samples. The ratio of tiludronic acid concentrations in drill versus reference samples ranged from 73% to 185% (mean: 124%), 65% to 208% (mean: 118%), and 26% to 110% (mean: 62%) respectively in the tuber coxae, 13th rib and cuboïd bone. In all but one horse, the highest concentrations in tiludronic acid were found in the tuber coxae, while the lowest values tended to be in the cuboïd bone at any time post-treatment. Tiludronic acid was still found in all bone samples 7 months after treatment. Discussion As previously reported with other tools, the drill tested in this study should permit to conveniently perform bone biopsies in the equine tuber coxae. This biopsy site would be the most appropriate for repeated sampling to dose tiludronic acid over time. This would help to design appropriate PK/PD studies with tiludronic acid in horses. This study also further confirms the long persistence of tiludronic acid in equine bone. [less ▲]

Fully automated heart rate variability assessment in dairy cows

in Acta Physiologica (2006, May), 187(Suppl 651), -16

Horses on pasture may be affected by equine motor neuron disease

in Equine Veterinary Journal (2006), 38(1), 47-51

Reasons for performing study: Equine motor neuron disease (EMND) was diagnosed in 3 horses maintained on lush, grass-based pasture. This contrasted with North American studies which identified limited or ... [more ▼]

Reasons for performing study: Equine motor neuron disease (EMND) was diagnosed in 3 horses maintained on lush, grass-based pasture. This contrasted with North American studies which identified limited or no access to green herbage as an important risk factor for EMND. Hypothesis: Grazing horses that have an apparently adequate intake of pasture herbage to meet normal equine vitamin E requirements can develop EMND. Methods: Owners of 32 European horses diagnosed with EMND completed a questionnaire regarding intrinsic, managemental, nutritional and environmental factors that could potentially be risk factors for EMND, and also regarding clinical signs, treatments and case outcome. Plasma/serum vitamin E data for these horses were supplied by the veterinarians. No control population was studied. Results: Thirteen of 32 horses (termed the 'grazing' group) had part- or full-time access to grass-based pasture at the onset of EMND (median duration at pasture 12 h/day, range 3-24 h). Five of these horses were at pasture for at least 23.5 h/day at the onset of EMND, 2 of which were at pasture for at least 23.5 h/day throughout the year. Despite grazing, all these horses had a low vitamin E status. The remaining 19 horses resembled those cases reported from North America, in that they had no or limited access to pasture. Conclusions and potential relevance: A diagnosis of EMND should not be discounted on the basis that a horse has access, even full-time, to lush grass-based pasture. Inadequate vitamin E intake was probably not the sole cause of either the EMND or the low vitamin E status in the grazing horses; the latter was probably the result of abnormal bioavailability or excessive utilisation of vitamin E. [less ▲]

Exercise and pharmacological stress echocardiography in healthy horses

in Equine Veterinary Journal. Supplement (2006), 37

REASONS FOR PERFORMING STUDY: Stress echocardiography could be a useful diagnostic test in horses suspected to suffer from exercise-induced myocardial dysfunction as a cause of exercise intolerance ... [more ▼]

REASONS FOR PERFORMING STUDY: Stress echocardiography could be a useful diagnostic test in horses suspected to suffer from exercise-induced myocardial dysfunction as a cause of exercise intolerance. OBJECTIVE: To evaluate the effect of treadmill exercise and pharmacological stress test on left ventricular echocardiographic parameters. METHODS: Echocardiography was performed in 2 groups of 5 healthy horses, either immediately after a near-maximal treadmill exercise (Group EXE) or during a pharmacological challenge (Group DOB) consisting of 35 microg/kg atropine, followed by incremental dobutamine infusion rates of 2-6 microg/kg bwt/min for 5 min duration each, which led to a cumulative dobutamine dose of 100 microg/kg. Left ventricular M-mode parameters were compared at rest and at heart rates of 80, 100, 110, 120 130, and 140 beats/min, within each group. RESULTS: In 2 horses of Group EXE, echocardiographic measurements were impossible at 140 and 130 beats/min, as their heart rates dropped too fast in the immediate post exercise period. In the remaining 3 horses image quality was not always satisfactory at heart rates of 130 and 140 beats/min. Systolic left ventricular parameters and fractional shortening measured at 130 and 140 beats/min were significantly different from values obtained at lower heart rates. Horses in Group DOB reached expected heart rates of 80 and 100 beats/min, after the administration of atropine and during a dobutamine infusion rate of 2 microg/kg bwt/min, respectively. Heart rates targets of 110, 120, 130, and 140 beats/min were reached at mean (+/- s.d.) dobutamine infusion rates of 2.8 +/- 0.4, 3.2 +/- 0.4, 4.0 +/- 0.7, 5 +/- 0.7 microg/kg bwt/min, respectively. Systolic left ventricular parameters and fractional shortening at heart rates of 110, 120, 130, and 140 beats/min, were significantly different from values obtained at lower heart rates. CONCLUSION: The pharmacological stress test induced changes in ventricular dimensions at heart rates of 80 to 140 beats/min. Using this test, high quality images can easily be obtained at heart rates of 140 beats/min. Conversely, in post exercise echocardiography, obtaining good quality images at heart rates of 130 and 140 beats/min is difficult, which limits use of the technique in routine clinical settings. POTENTIAL RELEVANCE: Further studies should demonstrate the potential of pharmacological stress test as a diagnostic tool in horses suffering from exercise-induced myocardial dysfunction. [less ▲]

Equine oesophageal obstruction : a retrospective study on 143 cases

in Proceedings of the 45th Congress of the British Equine Veterinary Association (2006)