Detection times of clodronic acid in horses with orthopedic disease.

Clodronic acid is designated as a controlled medication for competition horses by the International Federation for Equestrian Sports and, according to the International Federation of Horseracing Authorities, clodronic acid is not to be administered to racehorses younger than 3.5 years or within 30 days prior to a race. In this study, 35 horses involved in competition were treated with a single dose of 1.53 mg clodronic acid/kg bodyweight intramuscularly. Plasma samples were obtained before treatment and 10, 20, 30, and 40 days post-administration. Clodronic acid concentrations were measured using a validated method, and the data were fitted using a nonlinear mixed effects model. The estimated depletion half-life of clodronic acid was 10.6 days (inter-individual variability: 17.9%). Age, body weight, sex, disease severity, dose, training days, training, and competition did not significantly impact the depletion half-life. The percentage of horses predicted via simulation to have clodronic acid concentrations below the assay's limit of quantification of 1.0 ng/mL was 93.9% at day 30 and 99.4% at Day 40. This study provides rationale to the equestrian federations and horse racing authorities to reliably establish a detection time for clodronic acid, assisting equine veterinarians in recommending a competition withdrawal time for the horses under their care.

Long-term detection of clodronate in equine plasma by liquid chromatography-tandem mass spectrometry.

Clodronate is a non-nitrogen-containing bisphosphonate drug approved in equine veterinary medicine. Clodronate is prohibited for use in competition horses; therefore, to set up an appropriate control, detection times and screening limits are required. The quantitative method in plasma consisted of addition of chloromethylene diphosphonic acid as internal standard. Automated sample preparation comprised a solid phase extraction with weak anion exchange properties on microplate. After methylation of the residue with trimethyl orthoacetate, analysis was conducted by high-performance liquid chromatography-tandem mass spectrometry. Using a weighting factor of 1/(concentration)2 , good linearity was observed in the range of 1 to 500 ng/ml, with low limits of detection and quantification of 0.5 and 1 ng/ml, respectively. Precision and accuracy determined at four concentrations were satisfactory, with an error percentage less than 15%. Absence of carry-over and good stability of clodronic acid in plasma after a long-term storage at -20°C were verified. The method was successfully applied to the quantification of clodronic acid in plasma samples from horses administered with a single intramuscular administration of Osphos® at a mean dose of 1.43 ± 0.07 mg/kg. The observed detection time will be verified in a clinical population study conducted in diseased horses.

What Do We Know About Clodronate Now? A Medical and Veterinary Perspective.

There has recently been some controversy over the use of bisphosphonates in horses and some confusion regarding the different classes of bisphosphonates and the differences between the mechanism of actions and effects of each class. This review article explores the different bisphosphonate classes and their different effects and mechanisms of action based on research from both the human and equine veterinary fields. This collaborative review between veterinary surgeons and medical doctors describes the latest use of bisphosphonates in humans and horses, including safety aspects, and allows comparisons to be drawn between the two fields. Potential future uses of bisphosphonates are also discussed.

Isoflurane measurement error using short wavelength infrared techniques in horses: influence of fresh gas flow and pre-anaesthetic food deprivation.

OBJECTIVE: To quantify the isoflurane measurement error arising from the use of short wavelength infrared (IR) anaesthetic gas analysis during low flow anaesthesia in horses. STUDY DESIGN: Prospective clinical study. ANIMAL POPULATION: Sixty-four client-owned horses referred for elective or emergency surgery (age 1-16 years, body mass 400-650 kg). MATERIALS AND METHODS: Horses were divided into four groups based on duration of pre-anaesthetic food deprivation period (FDP) and fresh gas flow during anaesthesia: a high flow group with normal FDP (n = 16) and three groups with low flow and normal (n = 29), long (n = 5) or no (n = 14) FDP, respectively. Circuit isoflurane concentrations were measured simultaneously using a short wavelength (methane-sensitive) analyser (Datex Capnomac Ultima) and a long wavelength (methane-insensitive) analyser (Hewlett Packard M 1025 B) for at least 60 minutes. The difference between the readings of both analysers gave the isoflurane measurement error of short wavelength IR analysis, from which the circuit methane concentration was calculated. RESULTS: In the low flow groups, isoflurane measurement error increased over time, whereas in the high flow group, error remained constant after an initial rise in the first 15 minutes. The isoflurane measurement error was significantly lower (p < 0.005) in the high flow group compared with the low flow-normal FDP group from 15 to 60 minutes. Compared to the low flow - normal FDP group, isoflurane measurement error was significantly smaller (p < 0.001, from 15 to 60 minutes) in the low flow-long FDP group and significantly larger (p = 0.016, at 60 minutes) in the low flow-no FDP group. Within the low flow-no FDP group, values in colic cases did not differ from those in noncolic cases (p > 0.7). CONCLUSIONS: Isoflurane measurement using short wavelength IR absorption is inaccurate. The fresh gas flow and duration of pre-anaesthetic food deprivation influence the isoflurane measurement error during anaesthesia in horses. CLINICAL RELEVANCE: Short wavelength IR analysers are not reliable for isoflurane measurement during (low flow) anaesthesia in horses.