Blood lactate disappearance after maximal exercise in trained and detrained horses

The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thorough-bred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (V̇O_2max, ml kg⁻¹ min⁻¹), VLA4 (velocity at which blood lactate concentration was 4 mmol litre⁻¹); LA8 (lactate concentration [mmol litre⁻¹] during exercise at 8 m sec⁻¹), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rt_d). The trained horses had a significantly lower LA8 (2·1 ± 0·1 vs 6·5 ± 1 mmol litre⁻¹, P<0·01), higher VLA4 (9·8 ± 0·2 vs 5·8 ± 0·6 m sec⁻¹, P<0·01) and higher V̇0_2max (156·3 ± 3·8 vs 107·1 ± 3·9 ml kg⁻¹ min⁻¹, P<0·001). The value of Rt_d and the time of peak lactate concentration were not significantly different.     

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back‐extrapolated time zero plasma concentration was significantly lower and median plasma half‐life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.     

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.     

Anesthetic and cardiopulmonary effects of total intravenous anesthesia using a midazolam, ketamine and medetomidine drug combination in horses

The anesthetic and cardiopulmonary effects of midazolam, ketamine and medetomidine for total intravenous anesthesia (MKM-TIVA) were evaluated in 14 horses. Horses were administered medetomidine 5 microg/kg intravenously as pre-anesthetic medication and anesthetized with an intravenous injection of ketamine 2.5 mg/kg and midazolam 0.04 mg/kg followed by the infusion of MKM-drug combination (midazolam 0.8 mg/ml-ketamine 40 mg/ml-medetomidine 0.1 mg/ml). Nine stallions (3 thoroughbred and 6 draft horses) were castrated during infusion of MKM-drug combination. The average duration of anesthesia was 38 +/- 8 min and infusion rate of MKM-drug combination was 0.091 +/- 0.021 ml/kg/hr. Time to standing after discontinuing MKM-TIVA was 33 +/- 13 min. The quality of recovery from anesthesia was satisfactory in 3 horses and good in 6 horses. An additional 5 healthy thoroughbred horses were anesthetized with MKM- TIVA in order to assess cardiopulmonary effects. These 5 horses were anesthetized for 60 min and administered MKM-drug combination at 0.1 ml/kg/hr. Cardiac output and cardiac index decreased to 70-80%, stroke volume increased to 110% and systemic vascular resistance increased to 130% of baseline value. The partial pressure of arterial blood carbon dioxide was maintained at approximately 50 mmHg while the arterial partial pressure of oxygen pressure decreased to 50-60 mmHg. MKM-TIVA provides clinically acceptable general anesthesia with mild cardiopulmonary depression in horses. Inspired air should be supplemented with oxygen to prevent hypoxemia during MKM-TIVA.     

Effect of creatine supplementation on muscle metabolic response to a maximal treadmill exercise test in Standardbred horses

The aim of the present study was to investigate the effect of creatine (Cr) supplementation on muscle metabolic response in connection with a maximal treadmill exercise test, known to cause a marked anaerobic metabolic response and adenine nucleotide degradation. First, 6 Standardbred trotters performed a standardised maximal exercise test until fatigue (baseline test). The test used was an inclined incremental treadmill test in which the speed was increased by 1 m/s, starting at 7 m/s, every 60 s until the horse could no longer keep pace with the treadmill. After this baseline test, the horses were separated into 2 equal groups. One half received a dose of 25 g creatine monohydrate twice daily, and the other group were given the same dose of lactose (placebo). The supplementation period was 6.5 days, after which the maximal treadmill exercise test was performed again. A washout period of 14 days was allowed before treatments were switched between groups and a new supplementation period started. After this second supplementation period a new maximal exercise test was performed. After supplementation with creatine or placebo, horses were stopped after performing the same number of speed steps and duration of exercise as they had in the baseline test. Blood samples for analysis of plasma lactate, creatine (Cr), creatinine, hypoxanthine, xanthine and uric acid concentrations were collected at rest, during each speed step and during recovery. The total blood volume (TBV) was also determined. Muscle biopsies for analysis of muscle metabolites (adenosine triphosphate [ATP], adenosine diphosphate [ADP], adenosine monophosphate [AMP], inosine monophosphate [IMP], creatine phosphate [CP], lactate [La] and glycogen) were taken at rest, immediately post exercise and after 15 min recovery. The results showed no significant increase in plasma Cr or muscle total creatine concentration (TCr) after supplementation with Cr. At the end of exercise ATP and CP concentrations had decreased and IMP and lactate concentrations increased in muscle in all groups. Plasma lactate concentration increased during exercise and recovery and plasma uric acid concentration increased during recovery in all groups. No influence could be found in TBV after supplementation with creatine. These results show that creatine supplementation in the dosage used in this study had no influence on muscle metabolic response or TBV.     

Anesthesia of horses with a combination of detomidine, zolazepam, tiletamine, and isoflurane immediately after strenuous treadmill exercise.

OBJECTIVES: To evaluate effects of strenuous exercise in adult horses immediately before anesthesia and to determine whether prior exercise affects anesthesia induction, recovery, or both. ANIMALS: 6 healthy Thoroughbreds in good condition and trained to run on a treadmill, each horse serving as its own control. PROCEDURE: Horses ran on a treadmill until fatigued, then were sedated immediately with detomidine hydrochloride and anesthetized with a zolazepam hydrochloride-tiletamine combination. Anesthesia was maintained with isoflurane in oxygen for another 90 minutes. Blood samples were taken before, during, and after exercise and during anesthesia. RESULTS: During exercise, changes in heart rate, core body temperature, plasma lactate concentration, arterial pH, and PaCO2 were significant. Plasma ionized calcium concentration was lower after exercise, compared with baseline values, and remained lower at 30 minutes of isoflurane anesthesia. Compared with baseline values, plasma chloride concentration decreased significantly during anesthesia after exercise. Cardiac output during anesthesia was significantly lower than that during preexercise, but significant differences between experimental and control periods were not observed. Arterial blood pressure during anesthesia was significantly lower than that during preexercise and initially was maintained better during isoflurane anesthesia after exercise. Cardiac output and blood pressure values were clinically acceptable throughout anesthesia. CONCLUSION: Administration of detomidine hydrochloride followed by zolazepam hydrochloride-tiletamine appeared to be safe and effective for sedation and anesthesia of horses that had just completed strenuous exercise. CLINICAL RELEVANCE: Anesthetic given in accordance with this protocol can be used to anesthetize horses that are injured during athletic competition to assess injuries, facilitate first aid, and possibly allow salvage of injured horses.     

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats

Objective

To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L^–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.

Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol-medetomidine in dogs

This study compared anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol (TT), tiletamine-zolazepam-butorphanol-medetomidine (TTD), and tiletamine-zolazepam-butorphanol-medetomidine with atipamezole reversal 1 hour after TTD administration in dogs. All dogs received glycopyrrolate. All drug combinations effectively induced anesthesia within 5 minutes after IM injection. Duration of analgesia was 40 to 60 minutes. Recovery was smooth, but the overall quality of recovery was poorer in the TT group. Hypoxia occurred with some dogs in the TTD group at 5 minutes. TTD provided better analgesia with longer duration and better recovery quality compared with TT. Reversal of TTD with atipamezole was not effective in shortening recovery time.     

Pharmacokinetics and toxic effects of lithium chloride after intravenous adminstration in conscious horses

OBJECTIVE: To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. ANIMALS: 6 healthy Standardbred horses. PROCEDURE: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. RESULTS: Lithium elimination could best be described by a 3-compartment model for 5 of the 6 horses. Mean peak serum concentration was 0.561 mmol/L (range, 0.529 to 0.613 mmol/L), with actual measured mean serum value of 0.575 mmol/L (range, 0.52 to 0.67 mmol/L) at 2.5 minutes after administration of the last bolus. Half-life was 43.5 hours (range, 32 to 84 hours), and after 24 hours, mean serum lithium concentration was 0.13+/-0.05 mmol/L (range, 0.07 to 0.21 mmol/L). The 60-mmol dose of LiCl did not produce significant differences in any measured hematologic or biochemical variables, gastrointestinal motility, or ECG variables evaluated during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of lithium best fit a 3-compartment model, and clearance of the electrolyte was slow. Healthy horses remained unaffected by LiCl at doses that exceeded those required for determination of cardiac output. Peak serum concentrations were less than steady-state serum concentrations that reportedly cause toxic effects in other species.     

Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine

Nine Thoroughbred horses were assessed to determine the normal response of insulin, glucose, cortisol, plasma potassium (K) and erythrocyte K through conditioning and to exercise over 400 and 1,000 m. In addition, adrenaline, noradrenaline, cortisol, plasma K, erythrocyte K and L-lactate concentrations were evaluated in response to maximal exercise with and without the administration of acepromazine. Conditioning caused no obvious trends in plasma K, erythrocyte K, insulin or glucose concentration. Serum cortisol increased (P less than 0.05) from the initial sample at Week 1 to Weeks 4 and 5 (attributed to a response to training), and then decreased. During conditioning, three horses had low erythrocyte K concentrations (less than 89.3 mmol/litre). Further work is needed to define the significance of low erythrocyte K concentrations in the performance horse. In all tests maximal exercise increased plasma K, glucose and cortisol concentrations, whereas insulin and erythrocyte K concentrations decreased. Thirty minutes following exercise, plasma K and erythrocyte K concentrations returned to resting values; whereas glucose and cortisol concentrations continued to increase and the insulin concentration also was increased. The magnitude of the changes varied for pre-conditioned vs post-conditioned exercise tests and the duration of exercise. The administration of acepromazine prior to exercise over 1,000 m failed to alter the circulating noradrenaline and adrenaline concentrations in anticipation of exercise or 2 mins following exercise. Acepromazine administration, however, did cause lower L-lactate concentration 2 mins (P less than 0.03) and 30 mins (P less than or equal to 0.005) following exercise. Also, erythrocyte K showed a delayed return to baseline levels at 30 mins post exercise. Further evaluation of these trends may help explain the beneficial role acepromazine plays in limiting signs of exertional rhabdomyolysis when administered prior to exercise.     

Effects of N,N-dimethylglycine on cardiorespiratory function and lactate production in thoroughbred horses performing incremental treadmill exercise

In a crossover study, either a placebo paste or N,N-dimethylglycine was administered orally at a dose rate of 1.2 mg/kg twice daily for five days to six thoroughbred horses, with bodyweights ranging from 424 to 492 kg. Using previously determined regression equations for oxygen uptake (VO2) against speed for each horse, a standardised exercise test was given with speeds equivalent to fixed percentages of the maximum oxygen uptake (VO2max). The test consisted of two minutes at speeds equivalent to approximately 40 per cent and 50 per cent VO2max, and one minute at speeds that produced approximately 60, 70, 80, 90 and 100 per cent VO2max. During the last five seconds of each exercise stage, the values of VO2, carbon dioxide production (VCO2), heart rate, arterial blood and plasma lactate concentrations, arterial blood gases and pH were measured. Before and immediately after the exercise test, muscle biopsies were collected from the middle gluteal muscle to determine the muscle lactate concentrations. The administration of N,N-dimethylglycine produced no significant differences in any of the measured values, and it is concluded that the compound has no beneficial effects on cardiorespiratory function or lactate production in the exercising horse.     

The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats

ObjectiveTo 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.Study designFour treatments of alfaxalone were administered in sequential order.AnimalsEight healthy adult cats (four male; four female) weighing between 3.71 and 5.91 kg.MethodsCats 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 (PaO₂, PaCO₂) 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.ResultsAlfaxalone 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 PaO₂ 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.Conclusions and clinical relevanceAlfaxalone produced dose-dependent anesthesia, cardiorespiratory depression and unresponsiveness to noxious stimulation in unpremedicated cats. Hypoventilation and apnea were the most common side effects.     

A comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol- medetomidine in cats

Using a randomized crossover design, this study compared the anesthetic and cardiorespiratory effects of three intramuscular anesthetic combinations in seven 2-year-old cats: tiletamine-zolazepam (8 mg/kg) and butorphanol (0.2 mg/kg) (TT); tiletamine-zolazepam (3 mg/kg), butorphanol (0.15 mg/kg), and medetomidine (15 microg/kg) (TTD); or the TTD protocol plus atipamezole (75 microg/kg IM) given 20 minutes later to reverse medetomidine. Analgesia was assessed using algometry and needle pricking. All three combinations effectively induced anesthesia suitable for orotracheal intubation within 5 minutes after injection. Hemoglobin oxygen saturation was lower than 90% at least once in all three groups between 5 and 15 minutes after drug administration. Blood pressure and heart and respiratory rates were within normal ranges. Both TT and TTD appeared to be effective injectable anesthetic combinations. TTD provided significantly better analgesia with a longer duration than did TT. Atipamezole administration shortened the duration of analgesia and decreased blood pressure but did not shorten total recovery time.     

Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration

Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications.     

Pharmacokinetics of metronidazole in horses after intravenous, rectal and oral administration

Metronidazole pharmacokinetics in horses was studied after intravenous (i.v.), rectal (p.r.) and oral (p.o.) administration at 20 mg/kg using a triple crossover study design. Metronidazole mean+/-SD half-life was 196+/-39, 212+/-30 and 240+/-65 min after i.v., p.r. and p.o. administration, respectively. The metronidazole clearance was 2.8 (mL/min/kg) and the volume of distribution at steady state was 0.68 L/kg. The pharmacokinetic parameters calculated for metronidazole after administration of the drug by the various routes showed that bioavailability (74+/-18 vs. 30+/-9%) and maximum serum concentration (22+/-8 vs. 9+/-2 microg /mL) were significantly higher after p.o. administration compared with p.r. administration. There were no significant differences in mean absorption time (45+/-69 vs. 66+/-18 min) and the time to reach maximum serum concentration (65+/-36 vs. 58+/-18 min). The results indicated that p.r. administration of metronidazole to horses, although inferior to p.o. administration in terms of bioavailability, provides an alternative route of administration when p.o. administration cannot be used.     

Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min^?1 kg^?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.     

Pharmacokinetics of danofloxacin in horses after intravenous, intramuscular and intragastric administration

REASONS FOR PERFORMING STUDY: Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. OBJECTIVE: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. METHODS: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. RESULTS: Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2-compartment open model. The disposition of i.m. administered danofloxacin was best described by a one-compartment model. The terminal half-lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean +/- s.d. 88.48 +/- 11.10% and Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 0.21 +/- 0.07 mg/l. CK activity following i.m. dosing increased 3-fold over pre-injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. CONCLUSIONS: Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. POTENTIAL RELEVANCE: Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.