Effect of mixing dietary fibre (purified lignocellulose or purified pectin) and a corn meal on glucose and insulin responses in healthy horses

The aim of this study was to investigate the effect of the addition of a purified soluble (pectin) and insoluble (lignocellulose) fibre to a starchy meal on post‐prandial glucose and insulin responses in healthy horses. Four horses were fed in a randomized order three different diets: (i) cracked corn, (ii) cracked corn mixed with purified lignocellulose, and (iii) cracked corn mixed with purified pectin. Each diet was adjusted to a starch intake of 2 g/kg bodyweight (BW). Lignocellulose was aligned to an intake of 0.2 g/kg BW, and pectin was fed in a dosage of 0.1 g/kg BW. Each period consisted of a 10‐day acclimatization to the diet (fed once per day); during this time, the horses were fed 1.2 kg hay/100 kg BW/day. Blood was collected after each acclimatization period before and after the test meal was fed, without any hay. The increase in plasma glucose and insulin, peak values, and area under the curves were similar for all diets. The present findings suggest that adding purified soluble or insoluble fibre to a corn meal does not affect post‐prandial glucose and insulin responses in healthy horses. Feeding strategies for horses with a high energy requirement should include a starch reduction per meal, rather than the addition of purified fibre.     

Effect of feeding increasing quantities of starch on glycaemic and insulinaemic responses in healthy horses

The aim of this study was to investigate the effect of increasing the intake of starch on the glycaemic and insulinaemic responses of horses. A cross-over study design was used in which four horses were fed increasing amounts of a compound feed (0.5–3.5 kg) to provide 0.3, 0.6, 0.8, 1.1, 1.4 and 2 g starch/kg bodyweight (BW)/meal. The glycaemic response increased with starch intake (P < 0.05), while feeding <1.1 g starch/kg BW resulted in a lowered response, compared to when 1.1–2 g starch/kg BW was fed (P < 0.01). The results suggested that insulin responses may be more appropriate to define the effect of feeding different starch levels than glycaemic responses. A starch intake of <1.1 g/kg BW/meal produced only moderate glucose and insulin responses, even though highly processed cereals were used. It is therefore recommended that a starch intake of <1.1 g/kg BW/meal or a meal size of 0.3 kg/100 kg BW (starch content of 30–40%) is used for horses.     

Determination of Pasture Dry Matter Intake Rates in Different Seasons and Their Application in Grazing Management

Eight mature horses weighing 576 ± 32 kg (mean ± SD) were used to compare differences in pasture dry matter (DM) intake rate in October (period 1), February (period 2), and May (period 3). Horses were randomly assigned to a pair of adjacent 5 m × 5 m grazing cells containing nontoxic, endophyte-infected tall fescue. Horses had access to each cell for 4 hours. Pasture DM intake rate was estimated over the entire 8-hour period by measuring the pre- and postgrazing herbage mass within each cell and was expressed as kg DM/100 kg body weight (BW)/hr. Mean 8-hour DM intake rate in period 1 (0.17 ± 0.01 kg DM/100 kg BW/hr) was greater (P < .001) than for period 2 (0.09 ± 0.01 kg DM/100 kg BW/hr) and period 3 (0.11 ± 0.01 kg DM/100 kg BW/hr), but it was not different (P = .274) between periods 2 and 3. A second experiment using the same eight horses was conducted immediately after the first experiment, within each season, to determine whether the DM intake rates derived from the first experiment could be used along with estimates of maintenance digestible energy (DE) requirements and pasture DE concentrations to predict the amount of grazing time required for a horse to consume only its maintenance DE requirement and maintain zero BW change over a 6-week period. Grazing time necessary to maintain zero BW change was accurately predicted for period 1 only.     

Associations between meal size,gastric emptying and post‐prandial plasma glucose,insulin and lactate concentrations in meal‐fed cats

Plasma glucose and insulin concentrations are increased for 12–24 h in healthy cats following moderate‐ to high‐carbohydrate meals. This study investigated associations between gastric emptying time and post‐prandial plasma glucose, insulin and lactate concentrations in cats fed an extruded dry, high‐carbohydrate, moderate‐fat, low‐protein diet (51, 28, 21% metabolizable energy, respectively) once daily by varying meal volume. Eleven healthy, non‐obese, neutered adult cats were enrolled in a prospective study and fed to maintain body weight. Ultrasound examinations were performed for up to 26 h, and blood collections over 24 h after eating meals containing approximately 100% and 50% of the cats’ daily caloric intake (209 and 105 kJ/kg BW, respectively). Gastric emptying time was increased after a meal of 209 kJ/kg BW compared with 105 kJ/kg BW (median gastric emptying times 24 and 14 h, respectively; p = 0.03). Time for glucose to return to fasting was longer after the 209 kJ/kg BW meal (median 20 h; 25th and 75th percentiles 15 and 23 h, respectively) than the 105 kJ/kg BW meal (13, 12 and 14 h; p < 0.01); however, peak glucose was not higher after the 209 kJ/kg BW meal compared with the 105 kJ/kg BW meal [(mean ± SD) 6.6 ± 0.6 and 7.8 ± 1.2 mmol/l, respectively, p = 0.07]. Times for insulin to return to fasting were not significantly longer after the 209 kJ/kg BW meal than the 105 kJ/kg BW meal (p = 0.29). d ‐ and l ‐lactate concentrations were not associated with gastric emptying time or post‐prandial blood glucose and insulin. Based on results obtained, prolonged gastric emptying contributes to prolonged post‐prandial hyperglycemia in cats meal fed a high‐carbohydrate, low‐protein, dry diet and fasting times for cats’ meal‐fed diets of similar composition should be 14–26 h, depending on meal size.     

Postprandial Blood Glucose and Insulin Responses of Horses to Feeds Differing in Soluble Fiber Concentration

In humans, the consumption of soluble fibers reduces glycemic response after a meal. We hypothesized high soluble fiber diets would reduce and delay postprandial glucose and insulin responses in horses. In a 4 × 4 Latin square design experiment, four Quarter Horse geldings were adapted to diets containing orchardgrass hay (ORCH) or ORCH with 1 of 3 treatment ingredients: molassed sugar beet pulp (BEET), almond hulls (HULL), or steam-crimped oats (OATS). Blood was serially sampled for 6 hours after feeding 0.15% body weight (BW) of the treatment ingredient (meal test) or 1.1 g starch/kg BW from oats plus the treatment ingredient (starch test) to evaluate glycemic and insulinemic responses. Glycemic response during the meal test peaked between 60 and 90 min after feeding (P < .05) and tended to be altered by diet (P = .071) and diet × time (P = .076). Serum insulin was affected by diet (P = .008), time (P < .001), and diet × time (P < .001) during the meal test, with concentrations lower in ORCH compared with BEET and OATS (P < .05). In the starch test, glucose was lower (P < .05) in ORCH and HULL compared with BEET and insulin was lower (P = .046) in ORCH compared with BEET. In both tests, horses took longer (P < .05) to consume HULL, likely influencing postprandial responses. Future research integrating the functional properties of feeds with physiological responses will be necessary to elucidate how soluble fiber affects postprandial glucose metabolism in horses.     

Evaluation of Factors Contributing to Daily Within-Horse Variation of Plasma Alpha-Tocopherol Concentration

The current study was conducted to evaluate daily within-horse variation of plasma alpha-tocopherol concentration (TOC) (Experiment 1 [EXPT1]) and to determine the effect of a single meal on plasma TOC (Experiment 2 [EXPT2]). In EXPT1, venous jugular blood samples were collected from four pregnant (6–7 months of gestation), light horse mares (8.8 ± 2.9 years of age, mean ± SD; range, 5–11 years of age) between 7:30 AM and 8:30 AM, followed by eight hourly samples, and analyzed for plasma TOC. All horses were fed 5 kg dry matter (DM) grass hay 18 hours before sample collection and received no additional feed during the sampling period. Mean within-horse coefficient of variation for TOC was 3.5% ± 0.01%. In EXPT2, seven mature light horses, four mares and three geldings (4.9 ± 4.4 years of age, mean ± SD; range, 2–14 years of age), were randomly assigned to one of two treatments (fasted [FST; n = 7] or fed [FD; n = 7]), followed by reversal of treatments 24 hours later. At 7:30 AM, FD horses were fed 2.1 kg DM grain-mix concentrate (187 IU vitamin E/kg DM) plus 3.3 kg DM mixed-grass hay, whereas FST horses received no feed. Neither group received any feed for 18 hours before 7:30 AM. Venous jugular blood samples were collected at 10:30 AM from all horses and analyzed for plasma TOC. The mean (±SD) within-horse paired-treatment difference was not significant (0.05 ± 0.12 μg/mL). The results suggest that variation in within-horse plasma TOC is relatively small over an 8-hour period in fasting horses and is unaffected 3 hours after a hay grain meal.     

Role of cholecystokinin in the gastric motor response to a meal in horses

OBJECTIVE: To measure plasma cholecystokinin (CCK) activity and the effect of a CCK-1 receptor antagonist on accommodation of the proximal portion of the stomach, and subsequent gastric emptying, in horses after ingestion of high-fat or high-carbohydrate meals. ANIMALS: 6 healthy adult horses with gastric cannulas. PROCEDURES: In the first study, horses were offered a high-fat (8% fat) or a high-carbohydrate (3% fat) pelleted meal of identical volume, caloric density, and protein content. Related plasma CCK-like activity was measured by radioimmunoassay (RIA). In a separate experiment, a horse was fed a grain meal with corn oil and phenylalanine, and plasma CCK activity was assessed by bioassay. A second study evaluated the effect of a CCK-1 receptor antagonist, devazepide (0.1 mg/kg, IV), on gastric accommodation and emptying following a meal of grain supplemented with either corn oil (12.3% fat) or an isocaloric amount of glucose (2.9% fat). Gastric tone was measured by a barostat and emptying by the (13)C-octanoic acid breath test. RESULTS: No plasma CCK-like activity was detected by RIA or bioassay before or after ingestion of meals. Preprandial devazepide did not alter the gastric accommodation response but did significantly shorten the gastric half-emptying time and time to peak breath (13)CO(2) content with the glucose-enriched meal. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, CCK participates in regulating the gastric motor response to a meal. Compared with other species, horses may be more responsive to carbohydrate than fat. A vagovagal reflex most likely mediates this regulation, with CCK as a paracrine intermediary at the intestinal level.     

Phosphorus bioavailability in diets for growing horses

A study of phosphorus (P) metabolism was carried out using 12 month old Brasileiro de Hipismo breed of horses to determine the P bioavailability available from feeds commonly fed to horses in Brazil. Five different diets were formulated to contain approximately equivalent levels of crude protein and digestible energy, as well as to supply at least 22 g P/horse/day (NRC, 1989). All 5 diets contained 40% Bermuda coastal hay plus 60% concentrate. The 5 different concentrates contained: C1 (corn + cottonseed meal) C2 (corn grain + soybean meal) C3 (corn + sugarcane yeast), C4 (oat + cottonseed meal), and C5 (oat + soybean meal). The radioisotope ³²P was injected with 30 MB. Blood, feces and urine were collected for 7 days to evaluate endogenous fecal P and true absorption. Analysis of variance of P intake showed differences due to dietary effects (P < 0.05). Concentrate C3 had the lowest intake (79.68 mg/ kg BW). All of the diets produced positive P retention. Absolute values for P concentrations in plasma, urine, feces and endogenous feces did not vary between diets. Values for endogenous fecal P were independent of the level of P intake, so the correlation between P intake and P endogenous was not significant. P bioavailability values were 50.75; 40.98; 43.50; 51.03 and 57.68% for diets C1 through C5, respectively. However, differences in P bioavailability were found (P < 0.05) between diets. Diets C2 and C3 had lower P bioavailability than the other diets. The P bioavailability of all dietary treatments in this study exceeded NRC (1989) postulations of 35% true P absorption in diets not supplemented with inorganic P. The results of this study indicate that inorganic P supplementation is not needed for growing yearlings fed common Brazilian feeds. Considering the high cost of P supplementation and the risk of environmental P contamination, inorganic phosphorus supplementation for growing yearlings may not be required.     

Pharmacokinetics of low-dose methotrexate in horses

This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min⁻¹ kg⁻¹ (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg⁻¹ week⁻¹ may be safe and relevant in horses, although this has yet to be clinically confirmed.     

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.     

Pharmacokinetics and Effects of Alkalization after Intravenous Administration of Eltenac in Horses

Eltenac (ELT) [4-(2,6-dichlorophenyl)amino-3-thiophene] is a non-steroidal anti-inflammatory drug (NSAID) that was developed for veterinary use in horses and cattle. The pharmacokinetics of ELT was evaluated in horses at 0.5 mg/kg body weight (BW) after single IV injection after 5 days of repeated IV administration and after a single IV injection in horses previously subjected to 250 mg/kg BW of sodium bicarbonate (NaHCO₃) as an alkalization treatment. The aim was to determine whether blood and subsequent urinary alkalization could modify the pharmacokinetics of ELT. Drug quantification was performed with serum and urine using high performance liquid chromatography with UV-visible detection. The results were also integrated with cyclo-oxygenase-inhibition literature data to review the dosage scheme of ELT in horses. After a single intravenous administration, ELT was characterized by rapid distribution (mean t½_λ1 = 0.18 ± 0.07 hour) and a short elimination half-life (mean t½_λ2 = 2.9 ± 0.68 hour). The volume of distribution was small (V_dss = 253.51 ± 47.55 mL/kg), which is likely because of the high percentage of drug protein binding (approximately 97%). The AUC_0-∞ and Cl_B were 6.92 ± 0.84 h*μg/mL and 73.2 ± 10 mL/h/kg, respectively. Repeated administration did not cause either accumulation or modification of the pharmacokinetic profile. The in vitro effective concentrations were maintained for a 6-hour period. The alkalization procedure appeared to accelerate drug elimination, as ELT was quantifiable only for 6 hours; however, the drug clearance was not significantly modified. Thus, the administration of alkaline compounds to accelerate the elimination of ELT is not completely confirmed.     

Plasma disposition,faecal excretion and in vitro metabolism of oxibendazole following oral administration in horses

Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite in the in vitro study. Metabolism of OBZ to its metabolite in vitro was significantly inhibited by co-incubation with the cytochrome P450 inhibitor piperonyl butoxide. These results indicated that first-pass metabolism decreases OBZ bioavailability in horses. The in vitro metabolism of OBZ was significantly inhibited by piperonyl butoxide and this could be utilised to extend the exposure of nematodes to the parent molecule.     

Validation of the Postprandial Interleukin-1β Response in Horses Using Equine-Specific Antibodies

Interleukin (IL)-1β is a commonly studied proinflammatory cytokine, with relevance to arthritis, obesity, aging, and other inflammatory diseases of horses. Evaluating protein concentrations in plasma is a useful measurement for research in these areas of equine health. The objective of this research was to validate a commercially available enzyme-linked immunosorbent assay (ELISA) for equine IL1β and to compare concentrations with those previously published using an ELISA that is no longer available. The ELISA was assessed for linear parallelism and recovery using plasma from four healthy Standardbred mares. The assay was found to have linear parallelism for samples diluted 1:2, when the detection antibody concentration was 3 μg/mL. The average recovery of spiked IL1β was 98.9%. To compare concentrations, plasma was collected from six geldings at −0.5, 1, 2, and 4 hours after consumption of a meal high in starch and sugar (1.2 g/kg bodyweight). Consumption of 1.2 g of starch and sugar per kg of BW increased plasma IL1β concentrations 1 hour after feeding (P = .053). In conclusion, the commercially available ELISA is validated, with modifications, for use in equine plasma, and it detects a rise in plasma IL1β concentrations at 1 hour after meal consumption, a finding that is similar to previously reported data.     

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.     

Effect of feeding on the pharmacokinetics of oral minocycline in healthy adult horses

Minocycline is commonly used to treat bacterial and rickettsial infections in adult horses but limited information exists regarding the impact of feeding on its oral bioavailability. This study's objective was to compare the pharmacokinetics of minocycline after administration of a single oral dose in horses with feed withheld and with feed provided at the time of drug administration. Six healthy adult horses were administered intravenous (2.2 mg/kg) and oral minocycline (4 mg/kg) with access to hay at the time of oral drug administration (fed) and with access to hay delayed for 2 hr after oral drug administration (fasted), with a 7‐day washout between treatments. Plasma concentration versus time data was analyzed based on noncompartmental pharmacokinetics. Mean ± SD bioavailability (fasted: 38.6% ± 4.6; fed: 15.7% ± 2.3) and C_max (fasted: 1.343 ± 0.418 μg/ml; fed: 0.281 ± 0.157 μg/ml) were greater in fasted horses compared to fed horses (p < .05 both). Median (range) T_max (hr) in fasted horses was 2.0 (1.5–3.5) and in fed horses was 5.0 (1.0–8.0) and was not significantly different between groups. Overnight fasting and delaying feeding hay 2 hr after oral minocycline administration improve drug bioavailability and thus plasma concentrations.     

Pharmacokinetics and Effects of Alkalization During Oral and Intravenous Administration of Naproxen in Horses

The use of suitable therapeutic protocols is particularly important when extra-label drugs are used or when physiological parameters are modified, as in the case of the administration of alkaline substances to racehorses. The pharmacokinetics of naproxen (NAP), after both intravenous (iv) and oral administration of 10 mg/kg body weight (BW), was investigated in horses under normal metabolic conditions and in horses whose conditions were modified by the iv administration of 250 mg/kg BW of sodium bicarbonate (NaHCO₃). The hypothesis that blood and consequent urinary alkalization could modify NAP pharmacokinetics was evaluated. Drug quantification was performed on serum and urine using High Performance Liquid Chromatography (HPLC) with ultraviolet-visible detection. Results were also integrated with cycloxygenase (COX)-inhibition published data to suggest an appropriate schedule for NAP dosage in horses. After iv administration, NAP was rapidly distributed (t_1/2α: 0.71 ± 0.43 iv NaHCO₃ and 0.55 ± 0.62 hours No NaHCO₃), whereas its elimination was quite slow (t_1/2β: 6.74 ± 0.41 hours), particularly in iv NaHCO₃ animals (t_1/2β: 8.95 ± 1.37 hours). After oral treatments, NAP was more rapidly absorbed and elimination was slower in iv NaHCO₃ animals (t_1/2λ_z: 17.50 ± 6.66 vs. 7.17 ± 0.91 hours). The oral bioavailability of NAP was approximately 87% and 77% in No NaHCO₃ and iv NaHCO₃, respectively. Urinary excretion of the drug as a parent compound was low. The alkalization procedure did not anticipate the elimination of the acidic drug as expected, but it also influenced the absorption of the drug that was administered orally. The dosage scheme of 10 mg/kg BW iv or orally seems to be appropriate to produce an anti-inflammatory effect for 12 to 24 hours.     

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.     

Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses

OBJECTIVE: To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. ANIMALS: 6 healthy adult horses. PROCEDURE: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. RESULTS: No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.     

Factors Affecting the Rate and Measurement of Feed Intake for a Cereal-Based Meal in Horses

The rapid intake of high-cereal, low-roughage meals may cause gastrointestinal and behavioral disorders. We investigated some of the factors that can affect the rate of intake (ROI) in four separate studies. Study 1 investigated the effect of chaff length and addition rate on the ROI of oats. The ROI decreased as more chaff was added to the diet, attaining significance (P < .05, n = 6) at levels above 15% addition and reaching a plateau at ∼50%. This was independent of stalk length (1.4 cm vs. 4.1 cm). Study 2 showed that meal size (varying from 0.5 to 4 g/kg BW) did not affect the ROI for a cereal-based meal, nor was ROI altered by the addition of 10% molasses (n = 6). Study 3 demonstrated that ROI changed markedly over the course of a meal, commencing at an average rate of 74 g/minute for the first 5 minutes and decreasing to 15.8 g/minute after 30 minutes (n = 6). Study 4 examined the effects of breed, BW, exercise, and gender in 71 horses. In Clydesdales, BW affected ROI (P < .05), and Clydesdales had a faster ROI than Thoroughbreds of similar BW (81.8 ± 6.8 vs. 66.0 ± 3.35 g/minute; P < .05). Exercise level, age, and gender did not impact ROI significantly. The results highlight the effectiveness of feeding chaff to slow ROI and demonstrate the need for a standardized protocol if ROI is to be compared between different studies.     

Effects of gossypol from cottonseed meal and dietary vitamin E on the reproductive characteristics of superovulated beef heifers

Superovulated Hereford-Angus crossbred heifers (average 397 kg BW) were used to test the effect of feeding cottonseed meal (gossypol) and vitamin E on embryo quality and ovarian characteristics. Twenty-four heifers were assigned randomly to four treatments with six heifers per treatment. Treatments were the following dietary supplements: 1) SBM (soybean meal + 30 IU vitamin E/kg of diet DM); 2) SBM+E (soybean meal + 4,000 IU vitamin E x animal(-1) x d(-1)); 3) CSM (cottonseed meal + 30 IU vitamin E/kg of diet DM); and 4) CSM+E (cottonseed meal + 4,000 IU vitamin E x animal(-1) x d(-1)). Supplements based on cottonseed meal provided 43.5 g of total gossypol/d (37% negative isomer (-) and 63% positive isomer (+)). Blood samples were collected at the start of the experiment and every 3 wk thereafter up to 12 wk. Plasma a-tocopherol (alpha-T) concentration was affected by treatments (P < 0.05). Heifers supplemented with cottonseed meal had greater (P < 0.05) alpha-T concentration in plasma than heifers supplemented with soybean meal at each concentration of vitamin E. Supplementation at 4,000 IU vitamin E x animal(-1) d(-1) increased (P < 0.05) the concentration of a-T in plasma. Weight gain, hemoglobin and hematocrit were not affected by treatment. Erythrocyte osmotic fragility (EOF) increased (P < 0.05) in cottonseed meal-fed animals; however, EOF was lowered (P < 0.05) with vitamin E supplementation. Heifers fed CSM and CSM+E supplements had greater (P < 0.01) concentrations of (-)-, (+)-, and total-gossypol in plasma, corpora lutea (CL), liver, and endometrium than heifers fed SBM and SBM+E supplements. Tissue alpha-T concentration increased with increased dietary supplemental vitamin E, particularly in great amounts in the CL. Because there was no adverse effect of gossypol on superovulation response or embryo development despite concentrations of gossypol in endometrium that are toxic to embryos, it is likely that systems exist in the reproductive tract to limit gossypol toxicity.