The safety of high‐dose buprenorphine administered subcutaneously in cats

The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol‐specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine‐treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug‐related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats.     

Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight‐week‐old dogs

The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8‐week‐old Beagle dogs. Thirty‐two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28‐day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14‐day intervals (Days 84, 98, and 112). The study ended on Day 126. Treatment groups were as follows: Group 1: untreated, sham‐dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a dose of at least 5 and 1 mg/kg, respectively (1×); Group 3: afoxolaner/milbemycin oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3); and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least 25 and 5 mg/kg, respectively (5×). All dogs were examined for general health twice a day beginning on Day ‐14. Physical examinations, and blood collections for clinical pathology analysis and afoxolaner and milbemycin oxime plasma concentrations, were performed throughout the study. No afoxolaner/milbemycin oxime treatment‐related changes were observed in growth, physical variables, clinical pathology variables, or tissues examined histologically. No clinically relevant or statistically significant health abnormalities related to the administration of afoxolaner/milbemycin oxime were observed. No signs of macrocyclic lactone sensitivity were observed at any time during the study. Vomiting and diarrhea were observed sporadically across all groups including the controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft chewables were shown to be safe when administered repeatedly at up to 5× the maximum exposure dose in dogs as young as 8 weeks of age.     

Influence of Bacillus subtilis GCB‐13‐001 on growth performance,nutrient digestibility,blood characteristics,faecal microbiota and faecal score in weanling pigs

The present study investigated the influence of Bacillus subtilis GCB‐13‐001 on growth performance, nutrient digestibility, blood characteristics, faecal microbiota and faecal score in weanling pigs. A total of 120 weaning pigs [(Landrace × Yorkshire) × Duroc; 7.73 ± 0.75 kg (28 days of age)] were randomly allotted into three treatments according to their initial body weight (BW) and gender in a 6‐week experiment. There were 8 replication pens in each treatment, with five pigs/pen. Dietary treatment groups were as follows: (a) basal diet (CON), (b) CON + 0.1% Bacillus subtilis GCB‐13‐001 1 × 10⁸ CFU/kg (T1) and (c) CON + 0.1% Bacillus subtilis GCB‐13‐001 1 × 10⁹ CFU/kg (T2). Days 1 to 7, the BW and ADG with T2 treatment were higher (p < .05) than CON treatment, as well as F:G showed trends in linear reduction (p < .1). Days 8 to 21, the BW and ADG were improved (p < .05) in pigs offered T1 and T2 diets compared with CON diet. Days 22 to 42, BW and ADG were higher (p < .05) in pigs fed T2 diet than CON and T1 diets, and the pigs fed T1 diet had higher BW than CON treatment. Overall, the ADG with the T2 treatment was higher (p < .05) than that with the T1 and CON treatments, and pigs offered T1 treatment had higher (p < .05) ADG than CON treatment. Moreover, F:G ratio were significantly decreased (p < .05) by T2 treatment compared with CON treatment. The faecal Lactobacillus counts were improved, and E. coli counts were reduced (p < .05) in pigs fed T2 diet compared with CON at the end of the experiment. In conclusion, supplementation of 0.1% Bacillus subtilis GCB‐13‐001 1 × 10⁹ CFU/kg has shown a beneficial effect in improving BW, increase ADG, decrease F:G ratio.     

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.     

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (C_SS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min⁻¹ kg⁻¹, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min⁻¹ kg⁻¹, respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median C_SS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median C_SS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on C_SS (therapeutic drug monitoring) and treatment failure should be considered.     

Safety of orally administered,USP‐compliant levothyroxine sodium tablets in dogs

The safety of synthetic levothyroxine sodium tablets (Thyro‐Tabs® Canine; LLOYD , Inc.) in dogs was evaluated in a randomized, sham‐dose controlled, parallel‐group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg^?1 day^?1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose‐dependent increase in serum concentrations of total and free thyroxine with dose‐dependent suppression of the hypothalamic–pituitary–thyroid axis as evidenced by decreased serum thyroid‐stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose–response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs.     

A double‐blind,placebo‐controlled,randomized study to evaluate the weight gain drug,mirtazapine transdermal ointment,in cats with unintended weight loss

Mirtazapine is classified as a weight gain drug in cats, and the purpose of this study was to evaluate its efficacy in cats experiencing unintended weight loss. This was a multi‐center, double‐blind, placebo‐controlled, randomized clinical study in client‐owned cats ≥1 year of age, weighing ≥2 kg, with a documented loss (≥5%) in body weight. Cats were treated once daily with either 2 mg/cat mirtazapine transdermal ointment (n = 83) or placebo (n = 94) (Per Protocol population) applied to the inner surface of the pinna for 14 ± 3 days. Physical examination, body weight, complete blood count, serum chemistry, and urinalysis were performed prior to treatment and on Day 14. Changes in body weight between the mirtazapine and placebo groups were evaluated from Day 1 to Day 14 and compared using a two‐sample t test. The mean percent change in body weight was +3.9% (standard deviation ±5.4%) in the mirtazapine group and +0.4% (±3.3%) in the placebo group (p < 0.0001). The most common adverse event was mild erythema at the application site in 17.4% of placebo and 10.4% of mirtazapine‐treated cats. Application of mirtazapine transdermal ointment was well tolerated both topically and systemically and resulted in significant weight gain in cats experiencing unintended weight loss associated with various underlying diseases.     

Drug Efficacy of Terbinafine Hydrochloride (Lamisil®) During Oral Treatment of Cats,Experimentally Infected with Microsporum canis

Cats represent a primary source of Microsporum canis infections in humans. Terbinafine hydrochloride (Lamisil^®) is commonly used in the treatment of microsporosis in humans as its fungicidal action permits short periods of treatment. The aim of the present study was to estimate the efficacy of the drug in cats. Nine cats were experimentally infected with M. canis and treated with terbinafine hydrochloride at a dose of 10–20 mg/kg (once daily, SID; low‐dose group, LDG). Another nine cats were similarly infected and treated with 30–40 mg/kg SID (high‐dose group, HDG) and a further nine cats were also infected and left untreated (control group, CG). The general condition of the cats was observed daily and their clinical symptoms evaluated weekly. The cats recovery was monitored using the Wood's lamp illumination test and microscopic and fungal culture examinations. The general condition of the cats during the study was good. The cure rates of the LDG were not significantly different from the CG at any period during the treatment. However, the HDG cure rates differed significantly from the other two groups. After 109 days of treatment, when all nine cats of the HDG were healed, seven cats of the LDG and all the cats in the CG were still M. canis‐positive. This study shows that dosages of 10–20 mg/kg SID of terbinafine hydrochloride are not sufficient to terminate an experimental M. canis infection in cats within an acceptable period of time. Terbinafine hydrochloride can be used to treat dermatophytosis in cats, but a higher dosage, 30–40 mg/kg SID, should be used to achieve a cure.     

Fertility of lactating dairy cows inseminated with sex‐sorted or conventional semen after Ovsynch,Presynch–Ovsynch and Double‐Ovsynch protocols

The objective was to compare pregnancy per artificial insemination (P/AI) with conventional (CS) or sex‐sorted semen (SS) in dairy cows subjected to one of the three timed AI protocols. Cows (n = 356) were randomly assigned to synchronization with Ovsynch (OVS), Presynch–Ovsynch (PO) or Double‐Ovsynch (DO) and inseminated on Day 77 ± 3 postpartum with either frozen‐thawed SS (n = 182) or CS (n = 184) of the same bull. More cows were cyclic at the beginning of breeding Ovsynch increased (p < 0.01) with presynchronization and it was greater for DO than PO (OVS = 78.5%, PO = 85.1%, DO = 95.6%). Overall, P/AI for SS and CS increased with presynchronization (p < 0.05) on Days 31 (OVS = 35.5%, PO = 47.1%, DO = 48.3%) and 62 (OVS = 30.1%, PO = 43.8%, DO = 43.9%). Regardless of synchronization treatments, insemination with SS reduced P/AI (p < 0.02) on Days 31 (38.1% vs. 50.6%) and 62 (34.5% vs. 45.6%) compared with CS. No interaction was observed between synchronization treatment and type of semen for P/AI, although in cows receiving CS, P/AI was numerically greatest for PO (OVS = 42.0%, PO = 59.3%, DO = 49.0%), and in cows receiving SS, it was numerically greatest for those inseminated following DO (OVS = 27.9%, PO = 35.5%, DO = 47.6%). Thus, presynchronization improved P/AI in cows inseminated with sex‐sorted or conventional semen.     

Effect of Illicium verum or Eucommia ulmoides leaf extracts on the anti-stress ability,and mRNA and protein expression of Nrf2 and TNF-α in Duroc × Landrace × Yorkshire and Chinese native Licha-black nursery piglets

Plant extracts are considered to be an effective alternative to antibiotics in response to weaning stress in piglets. This study evaluated the effect of Illicium verum extracts (IVE) or Eucommia ulmoides leaf extracts (ELE) on growth performance, serum and liver antioxidant ability of nursery piglets, as well as the difference of IVE and ELE on Duroc × Landrace × Yorkshire (DLY) and Chinese native Licha-black (LCB) piglets. A total of 96 nursery piglets (48 DLY and 48 LCB piglets) with an average body weight of 11.22 ± 0.32 kg were randomly divided into four treatments in a 2 × 4 factorial design. Each treatment had four replicates with 3 DLY and 3 LCB piglets per replicate respectively. Treatments included: basal diet, basal diet + 500 mg/kg IVE, basal diet + 250 mg/kg ELE and basal diet + 50 mg/kg chlortetracycline (CHL). All piglets were housed individually for the 42 days trial period after 7 days adaptation. Results showed that there were significant interactions (p < .05) between piglets species and dietary treatments in average daily gain (ADG) and feed efficiency, serum and hepatic glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), hepatic integral optical density (IOD) of α-tumour necrosis factor (TNF-α), hepatic relative mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/TNF-α and protein expression of TNF-α. Regardless of piglets species, supplementation with IVE and ELE increased (p < .05) ADG and feed efficiency, T-SOD and GSH-Px in serum and liver, hepatic IOD of Nrf2, hepatic mRNA and protein expression of Nrf2/TNF-α. However, CHL treatment resulted in lower (p < .05) serum GSH-Px and hepatic mRNA and protein expression of Nrf2/TNF-α, and higher hepatic MDA and IOD of TNF-α. Compared to LCB, DLY piglets had higher (p < .05) ADG and feed efficiency, serum and hepatic MDA, and protein expression of TNF-α, but lower (p < .05) ADFI, liver index, serum and hepatic GSH-Px, hepatic IOD of TNF-α, mRNA expressions of Nrf2/TNF-α were observed. In conclusion, Illicium verum (500 mg/kg) and Eucommia ulmoides leaf (250 mg/kg) extracts can increase the growth performance and antioxidant ability of DLY and LCB piglets, while chlortetracycline produces undesirable side-effects on the antioxidant ability of DLY and LCB piglets. Illicium verum and Eucommia ulmoides leaf extracts produced different antioxidant effects in DLY and LCB piglets with the Chinese native Licha-black pig responding better than Duroc × Landrace × Yorkshire.     

Bioavailability of morphine,methadone, hydromorphone,and oxymorphone following buccal administration in cats

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time–concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7–49.5), 44.2 ± 7.9 (18.7–70.5), 22.4 ± 6.9 (6.4–43.4), and 18.8 ± 2.0 (12.9–23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.     

Pharmacokinetics of fentanyl,alfentanil, and sufentanil in isoflurane‐anesthetized cats

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End‐tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration–time data. A 3‐compartment model best fitted the concentration–time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady‐state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo‐SD (range)], and the terminal half‐life (min) [median (range)] were 0.25 ± 0.04 (0.09–0.34), 2.18 ± 0.16 (1.79–2.83), 18.6 ± 5.0 (15–29.8), and 151 (115–211) for fentanyl; 0.10 ± 0.01 (0.07–0.14), 0.89 ± 0.16 (0.68–1.83), 11.6 ± 2.6 (9.2–15.8), and 144 (118–501) for alfentanil; and 0.06 ± 0.01 (0.04–0.10), 0.77 ± 0.07 (0.63–0.99), 17.6 ± 4.3 (13.9–24.3), and 54 (46–76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half‐lives for fentanyl and alfentanil, longer than for sufentanil.     

The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8 mg/kg once daily for 14 days consecutive days

The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally with Cerenia^® tablets (Pfizer Animal Health) once daily for 14 consecutive days at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic analysis was performed on the plasma concentration data to measure the AUC_0–24 (after first and last doses), C_t (trough concentration—measured 24 h after each dose), C_max (after first and last doses), t_max (after first and last doses), λ_z (terminal disposition rate constant; after last dose), t_1/2 (after last dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in plasma was substantially greater after fourteen daily 8 mg/kg doses than after fourteen daily 2 mg/kg doses as reflected in the AUC_0–24 accumulation ratio of 4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg) saturate the metabolic clearance mechanisms and delay drug elimination. To determine the time to reach steady‐state maropitant plasma levels, a nonlinear model was fit to the least squares (LS) means maropitant C_t values for each treatment group. Based on this model, 90% of steady‐state was determined to occur at approximately four doses for daily 2 mg/kg oral dosing and eight doses for daily 8 mg/kg oral dosing.     

Effects of space allocations and energy levels on growth performance and nutrient digestibility in growing and finishing pigs

Two experiments were conducted to investigate effects of different space allocations and different dietary metabolizable energy (ME) levels on growth performance and nutrient digestibility in growing and finishing pigs. In experiment 1, a total of 84 growing pigs [(Yorkshire × Landrace) × Duroc] with an initial body weight (BW) of 27.10 ± 1.60 kg were used in a 5‐week trial. Pigs were blocked based on initial BW into a 2 × 2 factorial design with the following factors: (i) 0.60 or 0.80 m²/pig space allocations; and (ii) 3,400 or 3,550 kcal/kg ME of diets. In experiment 2, a total of 84 finishing pigs with an initial BW of 67.43 ± 1.97 kg were used in a 10‐week trial. Pigs were allotted based on initial BW into a 2 × 2 factorial design with the following factors: (i) 0.81 or 1.08 m²/pig space allocations; and (ii) 3,300 or 3,450 kcal/kg ME of diet. In experiment 1, high ME diet improved gain‐to‐feed ratio (G:F) in pigs with low space allocation but not in pigs in high space allocation (p < .05). Additionally, high ME diet increased apparent total tract digestibility (ATTD) of nitrogen in low space allocation but decreased ATTD of nitrogen in high space allocation (p < .05). In experiment 2, high ME diet improved average daily gain (ADG) and G:F in early‐finishing pigs with low space allocation but not in pigs with high space allocation (p < .05). In conclusion, the provision of high ME diets was not enough to overcome the reduction in growth performance due to low space allocation but can improve feed efficiency in growing pigs and daily gain and feed efficiency early‐finishing pigs.     

Effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor velagliflozin,a new drug with therapeutic potential to treat diabetes in cats

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta‐hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post‐D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.     

Impact of α‐amylase supplementation on energy balance and performance of high‐yielding dairy cows on moderate starch feeding

In dairy cows, exogenous α‐amylase is suggested to improve starch utilization and positively affect performance and health traits linked to energy balance and fertility. In a 1‐year feeding experiment, 421 cows were orally supplemented with α‐amylase (treatment: 12.5 g/kg dry matter (DM) addition rate to a concentrated feed) or non‐supplemented (control) on the basis of an ad libitum total mixed ration (TMR). Every cow was allocated to a high‐ (≥32 kg milk/day) or late‐lactation group (<32 kg milk/day), in which the TMR starch content was 220 ± 20.8 g/kg DM and 183 ± 24.8 g/kg DM, respectively. The energetic effect of α‐amylase supplementation seemed to be exclusively related to the high‐lactation stage (5–100 days in milk) in primiparous cows, where the daily milk yield was 32 ± 0.49 versus 31 ± 0.50 kg per cow in the treatment versus control group (P < 0.05). The pluriparous cows did not benefit from the supplementation that way. In neither primiparous nor pluriparous cows, was the milk composition, the fat‐to‐protein ratio, the somatic cell score, the backfat thickness, serum total bilirubin, β‐hydroxybutyrate and the fertility found to be systematically affected by α‐amylase supplementation.     

Effects of complex probiotic supplementation in growing pig diets with and without palm kernel expellers on growth performance,nutrient digestibility,blood parameters,fecal microbial shedding and noxious gas emission

In Experiment 1, a total of 100 growing pigs (Duroc × [Landrace × Yorkshire]) with an average initial body weight (BW) of 24.88 ± 1.57 kg were randomly allotted to 2 × 2 factorial arrangement with two concentrations of palm kernel expellers (PKE) in diets at 0% or 10%, and two concentrations of supplemental probiotics at 0 or 6.0 × 10⁷ colony‐forming units/kg. There were five replicate pens per treatment with five pigs per pen. In Experiment 2, eight barrows with average initial BW of 25.78 ± 0.19 kg were allotted to a replicated 4 × 4 Latin square design with four diets and four periods per square. Four experimental diets were the same as Experiment 1. In Experiment 1, dietary probiotic supplementation improved (P < 0.05) the average daily gain (ADG), nutrient digestibility and the fecal Lactobacillus counts. Furthermore, interactive effects (P < 0.05) between PKE and probiotics were observed on ADG and growth‐to‐feed ratio. In Experiment 2, an interactive effect (P < 0.05) of PKE and probiotics was observed in apparent ileal digestibility of nitrogen and some amino acids. In conclusion, dietary probiotics did not improve PKE utilization and the use of probiotics in non‐PKE‐containing diet was more favorable than in PKE‐containing diet.     

Ronidazole pharmacokinetics in cats following delivery of a delayed‐release guar gum formulation

Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum‐coated colon‐targeted tablets of RDZ and to determine the pharmacokinetics of this delayed‐release formulation in cats. Guar gum‐coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean C_max 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum‐coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady‐state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.     

Development of prediction equation for methane‐related traits in beef cattle under high concentrate diets

The objective of this study was to develop a prediction equation for methane‐related traits in beef cattle and evaluate this equation using datasets with different cattle breeds and roughage rates. Enteric methane emission (CH₄, l/day) was measured using open‐circuit respiration chambers. Dry matter intake (DMI, kg/day), body weight (BW, kg), daily gain (DG, kg), total digestible nutrients (TDN, %DMI), and roughage rate (Rrate, %) were used as independent variables, and methane‐related traits—CH₄, CH₄ per DMI (CH₄/DMI, l/kg), and methane conversion factor (MCF, %)—were used as dependent variables. The best‐fit equations to predict methane‐related traits using a total of 76 records were CH₄ = –676.7 + 0.04194 × BW + 29.88 × DMI + 7.883 × TDN + 4.367 × Rrate, CH₄/DMI = –52.24 – 1.193 × 10^–3 × BW – 5.905 × DG + 1.077 × TDN + 0.5008 × Rrate, and MCF = –11.43 – 5.308 × 10^–4 × BW – 1.223 × DG + 0.2336 × TDN + 0.1157 × Rrate. The predictive ability of the developed equations differed between roughage rates but not between breeds. For CH₄, the predictive ability of the developed equations was better compared with previously reported equations in the low roughage rate dataset, but not in the high roughage rate dataset. Our results suggest that the developed equations of methane‐related traits can be applied in beef cattle fed with low roughage diets.     

Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats,cats with chronic kidney disease,and cats with liver disease

Ondansetron, a 5‐HT₃ receptor antagonist, is an effective anti‐emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg ( mean 0.49 mg/kg , range 0.27–1.05 mg/kg ) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal–Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL·h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age‐matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats.