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The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-phase extraction, samples were analysed by liquid chromatography/electrospray ionisation tandem mass spectrometry in positive ionisation mode. The applied multiple reaction monitoring (MRM) method allowed the detection of SDO and TMP with a lower limit of detection of 0.03 ng/mL in plasma and 0.2 (SDO) and 0.4 ng/mL (TMP) in urine, respectively. In the present study, detection times for SDO were 15 days in plasma and 49 days in urine, respectively. TMP was detected for up to 7 days in plasma and up to 50 days in urine, respectively. The detection via the TMP metabolite 3-desmethyl-trimethoprim was possible for 70 days in urine. Detection times of the other confirmed metabolites N4 -acetylated sulfadoxine, hydroxytrimethoprim, trimethoprim-1-oxide and trimethoprim-3-oxide were significantly lower. In order to postulate reasonable screening limits (SLs) to control specific withdrawal times, a Monte Carlo simulation was performed for SDO. The proposed SL of 10 ng/mL SDO in blood and 300 ng/mL urine corresponds to a detection time of 4 days.

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RESUMEN

In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (IV) dose of 0.2 mg/kg DIA Plasma and urine samples were collected at specified intervals until 16 and 26 days post-administration, respectively. Samples were analysed by a sensitive liquid chromatography-electrospray ionization/tandem mass spectrometry method. DIA showed a triphasic elimination pattern in the horse. The mean plasma clearance of DIA was 5.9 ml/min/kg, and the plasma elimination half-life in the terminal phase was 19.9 h. Applying the Toutain model approach, an effective plasma concentration of DIA was estimated at 24 ng/ml, and irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were computed to 0.047 and 0.1 ng/ml, respectively. The detection time according to the European Horserace Scientific Liaison Committee (EHSLC), that is the time for which observed DIA plasma concentrations of all investigated horses were below the IPC was 10 days. Using Monte Carlo Simulations, it was estimated that concentrations of DIA in plasma would fall below the IPC 18 days after the DIA administration for 90% of horses. However, in the present study, a single administration of DIA could be detected for 24 days in urine via the presence of OXA, its dominant metabolite.

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Show jumping is a highly specialized equestrian discipline that requires technical skill but also power and fitness. Monitoring the horses' aerobic performance is therefore essential in order to verify whether the training has induced the desired cardiovascular and muscular adaptations. This study therefore aimed at evaluating the validity of non-specific and discipline-specific field exercise tests for objective evaluation of aerobic performance in show jumpers. For this purpose, data obtained from horses competing at Junior and Young Rider level during show jumping competitions as well as field exercise tests were retrospectively analyzed. The effect of the level of difficulty, the horses' age, the penalty score and the horses' previous level of performance on blood lactate concentrations after show jumping competitions (100 observations in 49 horses) was evaluated by linear mixed effects models (horse as random effect). Estimated marginal means significantly increased from 140 (4.1 mmol/L) to 150 cm (5.2 mmol/L) classes (P = 0.02). Furthermore, post-exercise lactate values significantly increased with the horses' age (P = 0.001). Another group of 12 horses performed a standardized incremental field exercise test on a track (SETtrack), a standardized show jumping course (SETcourse) and a standardized grid exercise (SETgrid) each on three consecutive days. Indices of aerobic performance, derived from the SETtrack [velocity at a heart rate of 140 bpm (V140) and at a lactate concentration of 2 mmol/L (V La2 )] were highly correlated with heart rate (V140: r = -0.75, P = 0.005; V La2 : r =-0.66, P = 0.02) and lactate (V140: r = -0.73, P = 0.02; V La2 : r = -0.72, P = 0.02) in response to SETcourse as well as heart rate during SETgrid (V140: r = -0.73, P = 0.02; V La2 : r = -0.76, P = 0.01). Subjective rating of muscular fatigue was significantly correlated to the mean heart rate during SETcourse (r = -0.64, P = 0.05) and SETgrid (r = -0.74, P = 0.02) but not to the aerobic indices calculated from SETtrack. Besides non-specific incremental field tests, performance monitoring in show jumpers should therefore also include discipline-specific tests that more closely reflect the internal load induced by show jumping competitions.