Measurement of C‐peptide concentrations and responses to somatostatin,glucose infusion,and insulin resistance in horses

Reasons for performing study: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C‐peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Hypothesis: A human double antibody radioimmunoassay (RIA) detects C‐peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C‐peptide i.v. Insulin and C‐peptide concentrations were measured in horses (n = 6) undergoing an insulin‐modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). Results: A human RIA was validated for use with equine sera. Endogenous C‐peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15–1.61) ml/min/kg bwt. Mean ± s.d. C‐peptide‐to‐insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 ± 1.95 prior to infusion to 1.03 ± 0.18 during the first 20 min following dextrose administration. Median C‐peptide and insulin concentrations were 1.5‐ and 9.5‐fold higher, respectively in horses with IR, compared with healthy horses. Conclusions: Endogenous C‐peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. Potential relevance: Both C‐peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.     

Pharmacokinetics of tobramycin following intravenous,intramuscular, and intra‐articular administration in healthy horses

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (C_max) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on C_max:MIC of 10.     

Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half‐life, volume of distribution at steady‐state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr^‐1 kg^?1, respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half‐life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3‐compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 μg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.     

Pharmacokinetics of single doses of maropitant citrate in adult horses

The neurokinin‐1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under‐recognized in horses. Use of NK‐1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC‐MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half‐life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half‐life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half‐life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.     

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half‐life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.     

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24‐hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2‐hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC₉₀ of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 μg/ml. For the 24‐hr dosing interval, the mean plasma penicillin concentration was >0.07 μg/ml. Five horses (72%) exceeded 0.06 μg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%–65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 μg/ml for a 24‐hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.     

Correlation of Plasma Insulin Concentration with Laminitis Score in a Field Study of Equine Cushing's Disease and Equine Metabolic Syndrome

This study aimed to investigate endocrinologic test values and the response to treatment of two commonly encountered causes of endocrinopathic laminitis, equine Cushing's disease (ECD) and equine metabolic syndrome (EMS), in a veterinary practice setting. In particular, the study aimed to determine whether insulin concentration correlated to the severity of clinical laminitis in horses with EMS or ECD. Twenty-five horses were included in the study and assigned to one of three groups: ECD (n = 6), EMS (n = 10), and controls (n = 9). Blood samples were collected at an initial visit and then at regular intervals for the next 12 months. Plasma concentrations of adrenocorticotropin (ACTH), cortisol, and insulin and serum concentrations of glucose and total thyroxine (T4) were obtained. Horses with ECD had significantly higher plasma ACTH concentrations than EMS horses or controls. Horses with EMS and ECD both had significantly higher plasma insulin concentrations than control horses, which was correlated with the Obel grade of laminitis (r = 0.63). After treatment, there was a trend for a reduction in plasma ACTH concentration in horses with ECD. A program of diet and exercise for horses with EMS resulted in reductions in both plasma insulin concentrations and bodyweight, which was variable, depending on the individual. There was a significant correlation between the change in plasma insulin concentration and Obel grade of laminitis (r = 0.69). This study has highlighted the importance of baseline plasma insulin concentration as a potential indicator of the susceptibility of horses to laminitis and the response to a program of diet and exercise.     

Pharmacokinetics of procaterol in thoroughbred horses

Procaterol (PCR) is a beta‐2‐adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography–mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady‐state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half‐life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.     

Seasonal Variation in Serum Concentrations of Selected Metabolic Hormones in Horses

Background: Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. Objective: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). Animals: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 laminitic horses residing at the same farm/stable were also studied. Methods: Prospective study of healthy and laminitic horses. Plasma/serum samples were analyzed for concentrations of hormones and glucose. Results: ACTH was the only analyte to show a discrete seasonal pattern, with concentrations in healthy and EMS horses frequently outside of the reference range (9–35 pg/mL) in August through October. Insulin was elevated (>40 μIU/mL) in EMS horses during most months and median serum glucose was generally higher in EMS horses (100 mg/dL, range, 76–163 mg/ dL) than in controls (94 mg/dL, range, 56–110 mg/dL), but no seasonal patterns for insulin or glucose were found. Conclusions and Clinical Importance: An increased ACTH concentration in horses in late summer or autumn should be interpreted with caution. In contrast, insulin concentration is maintained within the reference range throughout the year in healthy horses, thus an increased insulin concentration at any time of year should raise suspicions of EMS, ECD, or both.     

The pharmacokinetics of midazolam after intravenous,intramuscular, and rectal administration in healthy dogs

Intravenous benzodiazepines are utilized as first‐line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3‐way crossover design with a 3‐day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high‐pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL (C₀) and 0.20 ± 0.06 μg/mL (C_max), following IV and IM administration, respectively. Time to peak concentration (T_max) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.     

Pharmacokinetics of furosemide administered 4 and 24 hours prior to high‐speed exercise in horses

Furosemide is a diuretic agent used commonly in racehorses to attenuate the bleeding associated with exercise‐induced pulmonary hemorrhage (EIPH). The current study describes serum and urine concentrations and the pharmacokinetics of furosemide following administration at 4 and 24 hrs prior to maximal exercise. Eight exercised adult Thoroughbred horses received a single IV administration of 250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high‐speed treadmill. Blood and urine samples were collected at time 0 and at various times for up to 72 hrs and furosemide concentrations determined using liquid chromatography–tandem mass spectrometry. Serum furosemide concentrations remained above the LOQ (0.05 ng/ml) for 36 hrs in 3/8 and 1/8 horses in the 4‐ and 24‐hrs groups, respectively. Serum concentration data were best fit by a two‐compartment model. There was not a significant difference in the volume of distribution at steady‐state (0.594 ± 0.178 [4 hrs] and 0.648 ± 0.147 [24 hrs] L/kg) or systemic clearance (0.541 ± 0.094 [4 hrs] and 0.617 ± 0.114 [24 hrs] L/hrs/kg) between horses that were exercised at 4‐ and 24 hrs postdrug administration. The mean ± SD elimination half‐life was 3.12 ± 0.387 and 3.23 ± 0.407 hrs following administration at 4 and 24 hrs prior to exercise, respectively.     

Pharmacokinetics of thymoquinone in layer chickens following oral and intravenous administration

Thymoquinone (TQ) is the major constituent of Nigella sativa and known to possess a variety of pharmacological effects. This study was designed to evaluate the pharmacokinetic profile of TQ following oral (PO) and intravenous (IV) administration in layer chickens. The layer chickens were equally divided into two groups (six chickens in each group, total 12 chickens), and TQ was administered via PO and IV routes. For PO route, the dose was 20 mg/kg b.w. and for IV route, 5 mg/kg b.w. was administered, respectively. A sensitive and accurate High‐Performance Liquid Chromatography (HPLC) technique was validated for the quantification of TQ from plasma. The limit of detection (LOD) and limit of quantification (LOQ) were 0.02 µg/ml and 0.05 µg/ml, respectively with >80% recovery. Maximum plasma concentration (C_max) following PO and IV administration was 8.805 and 4.497 µg/ml, respectively, while time to reach at maximum concentration (T_max) was 1 and 0.1 hr, respectively. The elimination half‐lives were recorded as 1.02 and 0.978 hr, whereas the mean residence times were 1.79 and 1.036 hr following both PO and IV administration, respectively. The 85% PO bioavailability was indicative that TQ could be used for various therapeutic purposes in layer chickens.     

Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses

Reasons for performing study: Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Hypothesis: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals received 56 g supplement with 0.25 kg oats once daily for 16 weeks. The supplement contained chromium (5 mg/day as yeast), magnesium (8.8 g/day as oxide/proteinate), and other nutraceuticals. Insulin‐modified frequently sampled i.v. glucose tolerance tests were performed with hay provided at 0, 8 and 16 weeks, and insulin sensitivity was estimated by minimal model analysis. Physical measurements were collected at the same points. Horses were not exercised. Results: Hyperinsulinaemia (>30 µu/ml) was detected in 12 of 14 horses prior to treatment. Glucose and insulin data from one mare with clinical laminitis were excluded because of persistent pain. Mean ± s.d. insulin sensitivity was 0.64 ± 0.62 × 10^?4 l/min/mu prior to treatment for the remaining 13 horses. Time and treatment × time effects were not significant for any of the variables examined, with the exception of resting insulin concentrations, which significantly increased over time (P = 0.018). Health status remained the same. Conclusions: The supplement containing chromium and magnesium evaluated in this study did not alter morphometric measurements, blood variables, resting insulin concentrations or insulin sensitivity in laminitic obese horses. Potential relevance: Additional research is required to determine the appropriate use of chromium and magnesium supplements in horses.     

Intracellular free magnesium concentration in healthy horses

Equine metabolic syndrome (EMS) is a worldwide disease in horses that parallels human diabetes mellitus type 2. In both diseases, patients show an altered peripheral insulin sensitivity as a key feature. In humans, multiple studies have demonstrated the beneficial effect of magnesium supplementation on insulin sensitivity. However, serum magnesium levels vary and are therefore not a reliable indicator of the patients’ magnesium status. Determining the intracellular free magnesium concentration appears to be a more sensitive diagnostic indicator. In this study, the free intracellular magnesium concentration was measured using mag‐fura 2 spectrophotometry in blood lymphocytes in 12 healthy, non‐obese horses at 9 a.m., 12 a.m. and 4 p.m. to establish reference ranges according to a protocol designed for human blood lymphocytes. Additionally, the serum magnesium concentration was measured. In all horses, the total serum magnesium concentration was within the reference range. The mean free magnesium concentration in blood lymphocytes of all horses was 0.291 ± 0.067 mmol/L with no significant difference between the time points. The reference range for the free intracellular magnesium concentration in equine lymphocytes was set at 0.16–0.42 mmol/L. The established values are slightly lower than those in healthy humans. The designed protocol for the measurement of the intracellular free magnesium concentration might be an excellent research tool to assess the cellular magnesium status and to reliably diagnose an altered magnesium homeostasis in EMS. Further studies shall elucidate possible alterations in cellular magnesium status in horses with EMS.     

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (T_max) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.     

Pharmacokinetics and local tolerance of cefovecin sodium after intra‐articular administration in horses

Searching for new therapeutic options against septic arthritis in horses, this research was focused on the study of the kinetics and local side effects after the intra‐articular treatment of horses with cefovecin sodium. A single dose (240 mg) of the drug (Convenia^®) was administered into the radiocarpal joint of adult healthy horses (n = 6), and drug concentrations in plasma and synovial fluid were determined by high‐performance liquid chromatography (HPLC). Local tolerance was also studied based on the modification of different joint physiopathological parameters (pH, cellular, and protein concentration in synovial fluid). Although no clinically relevant joint damage was noticed, significant increases in the protein concentrations at 5 min and in the cellular concentration at 30 min after cefovecin administration were observed in the treated radiocarpal joints. The duration of the cefovecin above the minimal inhibitory concentration (MIC) ≤1 μg/mL was 28.80 ± 2.58 h in the radiocarpal joint and 16.00 ± 2.86 h in plasma. The results of this study showed that intra‐articular administration of cefovecin sodium in horses could be considered in the future to manage septic arthritis in horses, as it offers a good pharmacokinetic behavior and good local tolerance.     

Doxycycline levels in preocular tear film of horses following oral administration

Objective To determine the concentration of doxycycline in preocular tear film following oral administration in horses as a possible therapeutic modality for infectious and keratomalacic equine keratitis. Procedure Eight broodmares without ocular disease from a Thoroughbred breeding facility were included in this study. Each mare received 20 mg/kg of doxycycline by mouth once daily in the morning for five consecutive days. Tears were collected 1 h after doxycycline administration starting on day one of administration and continuing for 10 consecutive days. Doxycycline levels in the tears were measured using liquid chromatography with tandem mass spectrometric detection (LC-MS/MS). Results Doxycycline was present in the tears of each mare at low µg/mL levels with the highest concentration appearing on the third to fifth days (8.21–9.83 µg/mL). Doxycycline levels had fallen below quantifiable ranges by day 10. No systemic side-effects were noted in any of the horses included in this study. Conclusions Oral doxycycline is present in preocular tear film of normal horses with noninflamed eyes and may be useful as treatment in equine ulcerative keratomalacia. The oral dose listed was tolerated well by the horses in this study. The drug levels attained at 20 mg/kg once daily orally of doxycycline may aid in the treatment of corneal ulceration in horses, but further study is warranted.     

Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations

Reasons for performing study: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti‐inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. Objectives: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty‐three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half‐life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier‐disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC₅₀ and MIC₉₀ for many gram‐positive equine pathogens. Potential relevance: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC≤0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.     

The Effect of Feeding Two or Three Meals Per Day of Either Low or High Nonstructural Carbohydrate Concentrates on Postprandial Glucose and Insulin Concentrations in Horses

Eight mature idle gelding horses (mean body weight [BW], 558 ± 45 kg) were used in a replicated 2 × 2 Latin square design study. Horses received either two or three meals per day (MPD) for 7 days, of either a high (H; 43%; 215 g/100 kg BW) or low (L; 18%; 90 g/100 kg BW) nonstructural carbohydrate (NSC) concentrate feed to achieve four treatment groups: low NSC in two MPD (L2), low NSC in three MPD (L3), high NSC in two MPD (H2), and high NSC in three MPD (H3). On day 7 of the treatments, blood was collected before (baseline) and for 5 hours after feeding the morning meal (10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, and 300 minutes after feeding). Baseline insulin concentrations tended (P = .093) to be higher for horses fed high NSC than low NSC, and horses fed two MPD tended (P = .092) to have higher baseline insulin concentrations than horses fed three MPD. In addition, baseline glucose-to-insulin ratio (GIR) was higher in horses fed high NSC compared with low NSC (P < .001). Horses fed high NSC had higher area under the curve of insulin and higher peak insulin after feeding than those fed low NSC. These findings suggest that NSC content of a concentrate feed has an impact on baseline insulin and GIRs and on postprandial insulin concentrations. Meanwhile, the number (and therefore size) of MPD had fewer impacts on glucose metabolism.