Pharmacokinetics of zonisamide after oral single dosing and multiple-dose escalation administration in domestic chickens (Gallus gallus).

BACKGROUND: There are few effective drugs for treatment of seizures in avian species. OBJECTIVES: To investigate the pharmacokinetics and safety of zonisamide in chickens. METHODS: Phase 1: chickens (n = 4) received a single oral dose of zonisamide at 20 mg/kg. Blood samples were collected intermittently for 36 hr after dosing. Phase 2: chickens (n = 8) received zonisamide in a dose escalation protocol (20, 30, 60 and 80 mg/kg orally every 12 hr). The dose was increased weekly, and peak and trough blood samples were collected on Days 1, 3, and 7 each week. Two birds were randomly euthanized at the end of each week. Plasma zonisamide concentrations were analysed using a commercial immunoassay. Drug concentration vs. time data were subjected to non-compartmental pharmacokinetic analysis. RESULTS: For Phase 1, peak plasma zonisamide (Cmax ) was 15 ± 3 µg/ml at 2 ± 1 hr (Tmax ). The disappearance half-life was 6.5 ± 1 hr. Mean plasma concentrations remained within the (human) therapeutic range (10-40 µg/ml) for 6 hr. For Phase 2 of the study, plasma concentrations of zonisamide remained within or close to the recommended mammalian therapeutic range for birds in the 20 and 30 mg/kg dose. Area under the curve (AUC) and Cmax were dose dependent. Two birds developed immune-mediated haemolytic anaemia. CONCLUSIONS: Zonisamide appears to be a viable drug for use in chickens at a dose of 20 mg/kg orally every 12 hr.

Effect of dose and duration of FSH treatment on ovarian response in prepubertal calves.

The objective of the study was to determine relative effects of dose (200 or 350 mg) and duration (4 or 7 days) of superstimulatory treatment on the ovarian response in prepubertal calves. Calves with similar antral follicular counts at wave emergence (n = 24) were given eight doses of either 25 or 44 mg pFSH every 12 h for 4 days or 14 doses of either 14 or 25 mg pFSH for 7 days beginning at the time of follicular wave emergence and 12.5 mg of pLH im 12 h after the last FSH treatment. On Day 4 of pFSH treatment, calves given 14 mg had fewer follicles ≥3 mm than those given 25 mg (15.1 ± 1.9 and 27.9 ± 3.3, respectively; P = 0.04). At the end of treatment (24 h post-LH), number of follicles ≥9 mm was greater in calves of groups treated with 350 than 200 mg (13.5 ± 1.8 and 8.8 ± 1.3, respectively; P = 0.02) and calves of groups treated for 7 than 4 days (13.3 ± 1.8 and 9.0 ± 1.3, respectively; P = 0.03). The number of spontaneous ovulations was greater in calves of groups treated for 7 than 4 days as was the total number of ovulations (9.7 ± 0.9 and 6.9 ± 1.0, respectively; P ≤ 0.05). In summary, a dose of 25 mg of pFSH per treatment given twice daily for 7 days resulted in a greater ovarian response than other superstimulatory treatments in prepubertal calves.

Pharmacokinetics of multiple doses of chloramphenicol in fed adult horses.

To the authors' knowledge, there have been no studies evaluating the pharmacokinetics of chloramphenicol administered orally to horses at the currently recommended dose of 50 mg/kg PO q6 h for multiple days. The published antimicrobial susceptibility breakpoint is 8.0 ug/mL; it is unknown if this concentration is achievable at the recommended dose rate in horses. The aim of this prospective multi-dose pharmacokinetic study was to perform pharmacokinetic analysis of chloramphenicol after multiple doses. The authors hypothesize that the antimicrobial susceptibility breakpoint will not be reached. Seven healthy adult horses were administered 50 mg/kg chloramphenicol base tablets PO q6 h for 4 days. Blood was collected via venipuncture daily at 4 and 6 h after administration for the first 15 doses. After the 16th dose, an IV catheter was aseptically placed in the right jugular vein and blood was collected at regular intervals for pharmacokinetic analysis. Maximum chloramphenicol concentration was variable between horses (2.1-42.7 µg/mL). The highest average chloramphenicol concentration was just below the susceptibility breakpoint at 7.7 ug/mL while the lowest was well below the breakpoint at 1.5 ug/mL. On average, the time above 8.0 µg/mL was 75 min, considerably less than the recommended 50% of the dosing interval. When chloramphenicol is administered at a dose of 50 mg/kg PO q6 h in horses, the highest reliably achievable steady state concentration for at least half of the dosing interval is 2.0 µg/mL. The established susceptibility breakpoint of 8.0 ug/mL is not achievable in adult horses, and should be re-evaluated.

The usefulness of short-course prednisolone during the initial phase of an elimination diet trial in dogs with food-induced atopic dermatitis.

BACKGROUND: Food allergy is a possible cause of atopic dermatitis (AD) in dogs; it is typically diagnosed following an eight-week elimination diet trial (EDT) and a provocation with the original diet. This lengthy procedure is difficult for owners and its interpretation may be unclear. HYPOTHESIS/OBJECTIVES: To test the effect of prednisolone used in the first weeks of an EDT in order to reduce the total time period for diagnosis. The goal was to perform food challenges earlier than after the traditionally recommended eight weeks. ANIMALS: Fifty-three dogs with AD were included in the study. METHODS AND MATERIALS: All dogs were fed a commercially available extensively hydrolyzed protein-based commercial pet food and treated with prednisolone for at least two weeks to control pruritus and inflammation. Dogs were challenged two weeks after prednisolone finished, provided that no flare had occurred. Dogs with relapsing signs were fed the hydrolyzate for at least eight weeks with or without further prednisolone treatment. RESULTS: Ten of 53 dogs (19%) had no relapse after two weeks off prednisolone: they were subsequently challenged with their regular food, had a relapse of signs and were diagnosed with a food-induced AD within four to six weeks of starting the EDT. In the other dogs, signs remained uncontrolled without prednisolone or relapsed rapidly after its discontinuation: they were considered nonfood-allergic after an eight week EDT. CONCLUSION AND CLINICAL IMPORTANCE: This study demonstrates that a shorter EDT is possible if the allergic pruritus and inflammation are initially controlled with a short course of glucocorticoids. This shortened trial is likely to improve owner adherence and facilitate the diagnosis of food allergy.

Effects of d-cloprostenol administrations with 7.5 and 11.5-day intervals between administrations on pregnancy rates after artificial insemination in estrous cyclic dairy goats.

This study was conducted to evaluate effects of two administrations of d-cloprostenol at different intervals to synchronize the time of estrus and ovulation among estrous cyclic goats. In Experiment 1, 32 does were treated with 30 µg d-cloprostenol at 7.5 (T7.5, n = 16) or 11.5-day (T11.5, n = 16) intervals. In Experiment 2, the same treatments were administered and there was AI of the does (T7.5, n = 40 and T11.5, n = 38). In Experiment 1, ultrasonic assessments of ovaries were conducted at the time of the second administration of d-cloprostenol, every 12 h until detection of ovulation, and 7 days after estrous onset to detect the corpora lutea, as well as for pregnancy diagnosis 40 days after AI. In Experiment 1, the estrous response (90.6%, 29/32) was similar (P > 0.05) in both groups. Diameter of the largest follicle at the time of administration of the second dose was larger (P = 0.01) in the T7.5 than T11.5 group (7.0 compared with 5.7 mm), while the values for ovarian variables were similar (P > 0.05). In Experiment 2, the greatest (P < 0.001) synchrony in timing of initiation of estrus in does (T7.5 = 83.3% and T11.5 = 50.0%) occurred after the second day (36-48 h). The pregnancy rate tended (P = 0.0836) to be greater for does in the T7.5 (71.4%, 40/56) than T11.5 (55.6%, 30/54) group. With use of both protocols, there were acceptable estrous synchronization and pregnancy rates in estrous cyclic dairy goats.

Administration of certain sedative drugs is associated with variation in sonographic and radiographic splenic size in healthy cats.

Ultrasonography and radiography are standard diagnostic tests for cats with suspected splenic disease, however published information on outside sources of variation are currently lacking. The purpose of this prospective, randomized, crossover group study was to evaluate effects of common sedative drugs on the sonographic and radiographic characteristics of the spleen in healthy cats. Fifteen healthy adult research cats were randomly assigned into one of three groups corresponding to different sequences of administration of five sedative drugs/drug combinations (acepromazine; butorphanol; dexmedetomidine; midazolam and butorphanol (MB); and dexmedetomidine, butorphanol, and ketamine (DBK)), administered at 1-week intervals. At each visit, three-view abdominal radiographic and ultrasonographic examinations were performed prior to sedation and repeated 15-30 min and 2-3 h post sedation. Two board-certified radiologists (one ACVR and one ACVR/ECVDI) evaluated the anonymized and randomized images. Acepromazine resulted in significantly increased sonographic and radiographic splenic measurements from baseline, which remained significantly increased 2-3 h post sedation. The mean magnitude of this change ranged from 0.9 mm (tail height, SD 1.4 mm) to 1.8 mm (body height, SD 1.7 mm) for ultrasound, and was 2.2 mm (ventrodorsal width, SD 2.3 mm) for radiographs. With butorphanol, there was no significant change in splenic size. For dexmedetomidine, MB, and DBK, there was a trend toward increased splenic size from baseline to the first post-sedation timepoint, which was statistically significant for radiographic measurements, although not for ultrasound. Findings indicated that acepromazine should be avoided prior to imaging while butorphanol may be used when sedation is needed in cats presenting for potential splenic disease.

Hyponatremia in dogs and cats.

OBJECTIVE: To review the pathophysiology, diagnostic approach, and treatment recommendations for hyponatremia in dogs and cats. ETIOLOGY: Hyponatremia almost always results from an increase in total body water (TBW), and not from loss of sodium. Abnormalities in antidiuretic hormone (ADH) are commonly part of the etiology of hyponatremia. DIAGNOSIS: Diagnosis of hyponatremia focuses on the cause of the increase of TBW. Assessment of the patient's volume status and measurement of urine sodium concentration are important factors. Measurement or calculated estimation of plasma osmolality can also guide the assessment of hyponatremia. THERAPY: Too rapid correction of serum sodium can precipitate osmotic demyelination syndrome. As a general rule, serum sodium concentration should be raised ≤10 mmol/L over 24 hours, but rapid increases in serum sodium are indicated if neurologic abnormalities are evident. Serum sodium can be increased using hypertonic saline, with dosing based on the patient's calculated sodium deficit. Treatment of the underlying cause of water ingestion or retention is also required to fully resolve hyponatremia. PROGNOSIS: Mortality rates are significantly higher in dogs and cats with hyponatremia compared to those with normal serum sodium concentrations, even in patients with mild hypontremia (<5 mmol/L below the lower value of the reference interval). Hyponatremia is also associated with increased risk of death if present during specific disease states in dogs.

African animal trypanosomosis (nagana) in northern KwaZulu-Natal, South Africa: Strategic treatment of cattle on a farm in endemic area.

African animal trypanosomosis (AAT) is caused by several species of the genus Trypanosoma, a parasitic protozoan infecting domestic and wild animals. One of the major effects of infection with pathogenic trypanosome is anaemia. Currently, the control policies for tsetse and trypanosomosis are less effective in South Africa. The only response was to block treat all infected herds and change the dip chemical to one which controls tsetse flies during severe outbreaks. This policy proved to be less effective as demonstrated by the current high level of trypanosome infections in cattle. Our objective was to study the impacts of AAT (nagana) on animal productivity by monitoring the health of cattle herds kept in tsetse and trypanosomosis endemic areas before and after an intervention that reduces the incidence of the disease. The study was conducted on a farm in northern KwaZulu-Natal which kept a commercial cattle herd. There was no history of any cattle treatment for trypanosome. All cattle were generally in poor health condition at the start of the study though the herd received regular anthelminthic treatment. A treatment strategy using two drugs, homidium bromide (ethidium) and homidium chloride (novidium), was implemented. Cattle were monitored regularly for 13 months for herd trypanosomosis prevalence (HP), herd average packed cell volume (H-PCV) and the percentage of the herd that was anaemic (HA). A total of six odour-baited H-traps were deployed where cattle grazed from January 2006 to August 2007 to monitor the tsetse population. Glossina brevipalpis Newstead and Glossina austeni Newstead were collected continuously for the entire study period. High trypanosomes HP (44%), low average H-PCV (29.5) and HA (24%) were rerecorded in the baseline survey. All cattle in the herd received their first treatment with ethidium bromide. Regular monthly sampling of cattle for the next 142 days showed a decline in HP of 2.2% - 2.8%. However, an HP of 20% was recorded by day 220 and the herd received the second treatment using novidium chloride. The HP dropped to 0.0% and HA to 0.0% by day 116 after the second treatment. The cow group was treated again by day 160 when the HP and HA were 27.3% and 11%, respectively. The same strategy was applied to the other two groups of weaners and the calves at the time when their HP reached 20%. Ethidium and novidium treatment protected cattle, that were under continuous tsetse and trypanosomosis challenge, for up to 6 months. Two to three treatments per year may be sufficient for extended protection. However, this strategy would need to be included into an integrated pest management approach combining vector control for it to be sustainable.

The frequency of oral famotidine administration influences its effect on gastric pH in cats over time.

BACKGROUND: Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown. OBJECTIVES: To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2. ANIMALS: Sixteen healthy cats. METHODS: Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance. RESULTS: Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day.

Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 5-Discontinuation of anticoagulant therapy in small animals.

OBJECTIVES: To systematically evaluate the evidence supporting the timing and mechanisms of permanent or temporary discontinuation of antiplatelet or anticoagulant medications in small animals DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality (poor, fair, or good), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. SETTINGS: Academic and referral veterinary medical centers. RESULTS: Databases searched included Medline via PubMed and CAB abstracts. Two specific courses of inquiry were pursued, one focused on appropriate approaches to use for small animal patients receiving antiplatelet or anticoagulant drugs and requiring temporary discontinuation of this therapy for the purposes of invasive procedures (eg, surgery), and the other aimed at decision-making for the complete discontinuation of anticoagulant medications. In addition, the most appropriate methodology for discontinuation of heparins was addressed. CONCLUSIONS: To better define specific patient groups, a risk stratification characterization was developed. It is recommended to continue anticoagulant therapy through invasive procedures in patients at high risk for thrombosis that are receiving anticoagulant therapy, while consideration for discontinuation in patients with low to moderate risk of thrombosis is reasonable. In patients with thrombosis in whom the underlying cause for thrombosis has resolved, indefinite treatment with anticoagulant medication is not recommended. If the underlying cause is unknown or untreatable, anticoagulant medication should be continued indefinitely. Unfractionated heparin therapy should be slowly tapered rather than discontinued abruptly.

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.

Evaluation of intravenous and subcutaneous administration of a novel, excipient-free, nanoparticulate formulation of paclitaxel in dogs with spontaneously occurring neoplasia.

Carriers used to solubilize taxane chemotherapy drugs cause severe hypersensitivity. Nanoparticle formulations can provide improved dissolution and bioavailability of taxanes. Thus, a nanoparticulate, excipient-free formulation of paclitaxel (CTI52010) was evaluated in tumour-bearing dogs with intravenous and subcutaneous delivery. Tumour-bearing dogs were treated with intravenous CTI52010 using a modified rapid dose escalation scheme. Subcutaneous administration was then planned for a small cohort of dogs for comparison. For both groups, serial blood samples were collected after first dosing for pharmacokinetic analysis by LCMSMS. Tumour response was measured using RECIST criteria. Toxicity was recorded using VCOG-CTCAEv1.1. Fifteen dogs were treated with intravenous delivery at increasing dosages (80-136 mg/m2 ), with one objective response in the urethral component of a prostatic carcinoma (probable transitional cell carcinoma) and four dogs with durable stable disease (two carcinomas, two sarcomas). Pharmacokinetic data indicate a rapid initial clearing of the drug from serum followed by an extended elimination half-life, similar to normal dogs and suggesting reticuloendothelial clearance. Parameters and toxicity were highly variable and a maximally tolerated dosage could not be reliably confirmed. Three dogs were treated with subcutaneous delivery and no drug was detected in circulation, resulting in termination of the study. This novel formulation of paclitaxel is well tolerated in dogs and no unique toxicity or hypersensitivity was noted. The preliminary responses suggest biologic activity. The lack of systemic absorption after subcutaneous administration suggests a possible role for intratumoural anticancer therapy.

Pharmacokinetics and pharmacodynamics of mycophenolic acid in healthy cats after twice-daily intravenous infusion of mycophenolate mofetil for three days.

OBJECTIVE To evaluate the plasma disposition of mycophenolic acid (MPA) and its derivatives MPA glucuronide and MPA glucoside after twice-daily infusions of mycophenolate mofetil (MMF) in healthy cats for 3 days and to assess the effect of MMF administration on peripheral blood mononuclear cell (PBMC) counts and CD4+-to-CD8+ ratios. ANIMALS 5 healthy adult cats. PROCEDURES MMF was administered to each cat (10 mg/kg, IV, q 12 h for 3 days). Each dose of MMF was diluted with 5% dextrose in water and then administered over a 2-hour period with a syringe pump. Blood samples were collected for analysis. A chromatographic method was used to quantitate concentrations of MPA and its metabolites. Effects of MMF on PBMC counts and CD4+-to-CD8+ ratios were assessed by use of flow cytometry. RESULTS All cats biotransformed MMF into MPA. The MPA area under the plasma concentration-time curve from 0 to 14 hours ranged from 14.6 to 37.6 mg·h/L and from 14.4 to 22.3 mg·h/L after the first and last infusion, respectively. Total number of PBMCs was reduced in 4 of 5 cats (mean ± SD reduction, 25.9 ± 15.8% and 26.7 ± 19.3%) at 24 and 48 hours after the end of the first infusion of MMF, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Plasma disposition of MPA after twice-daily IV infusions for 3 days was variable in all cats. There were no remarkable changes in PBMC counts and CD4+-to-CD8+ ratios.

Safety of lotilaner flavoured chewable tablets (CredelioTM) after oral administration in cats.

BACKGROUND: Lotilaner is a new member of the isoxazoline class for treatment of flea and tick infestations in cats. This laboratory study with lotilaner vanilla-yeast flavoured chewable tablets (CredelioTM, Elanco) investigated the safety in healthy kittens starting at 8 weeks of age in a randomized, blinded, parallel-group design. Lotilaner tablets were given orally once a month over eight months at one, three and five times the upper level of the maximum recommended dose range (26 mg/kg). METHODS: The safety of lotilaner flavoured chewable tablets was assessed in healthy kittens when administered orally every 4 weeks for 8 months at the highest recommended dose rates, i.e. 1× (26 mg/kg) and at elevated dose rates, i.e. 3× (78 mg/kg) and 5× (130 mg/kg). Sixteen male and 16 female healthy 8-week-old kittens, with a mean body weight of 0.79 kg and 0.75 kg, respectively, were randomized to an untreated control group or lotilaner groups at dose rates of 26 mg/kg (1×), 78 mg/kg (3×), or 130 mg/kg (5×) every four weeks over eight months. The control group was sham-dosed. All animals were fed within 30 minutes prior to treatment. Safety assessment included general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations, electrocardiographic (ECG) and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, organ macroscopic and microscopic examinations. RESULTS: Systemic exposure to lotilaner was confirmed during the course of the study in all treated animals with the exception of the control group. No treatment-related effects were seen on daily clinical observations, food consumption (wet), ophthalmoscopic, physical/neurological and microscopic examinations. Statistically significant differences were recorded in some of the clinical pathology parameters, body weights, food consumption (dry), electrocardiograms, and organ weights, but none of the recorded observations was considered to be of clinical relevance. CONCLUSIONS: Lotilaner, when administered once monthly over eight months at the highest recommended dose and overdoses of three- and five-fold, to 8-week-old healthy kittens, is well tolerated.

Comparison of two intravenous anesthetic infusion regimens for alfaxalone in cats.

OBJECTIVE: To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L-1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: A group of six healthy, adult male neutered cats. METHODS: Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for drug administration. An IV bolus of alfaxalone (2 mg kg-1) was administered, followed by either 0.2 mg kg-1 minute-1 for 240 minutes (single infusion; SI) or 0.4 mg kg-1 minute-1 for 10 minutes, then 0.3 mg kg-1 minute-1 for 30 minutes, and then 0.2 mg kg-1 minute-1 for 200 minutes (3-step infusion; 3-step). Plasma alfaxalone concentration was measured at six time points during the infusions. Measures of performance were calculated for each infusion regimen and compared using the paired Wilcoxon signed-rank test. RESULTS: Median (range) absolute performance error, divergence, median prediction error and wobble were 15 (8-19)%, -8 (-12 to -6)% hour-1, -12 (-19 to -7)% and 10 (8-19)%, respectively, in the SI treatment, and 6 (2-16)%, 0 (-13 to 2)% hour-1, 1 (-16 to 4)% and 4 (3-6)% respectively, in the 3-step treatment and were significantly smaller in the 3-step treatment than in the SI treatment. CONCLUSION AND CLINICAL RELEVANCE: After IV administration of a bolus dose, a 3-step infusion regimen can better maintain stable plasma alfaxalone concentrations close to the target concentration than a single constant rate infusion.

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats.

BACKGROUND: Multiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats. OBJECTIVE: Evaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats. ANIMALS: Nine healthy privately owned cats, body weight ≥ 5 kg METHODS: Extended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats. RESULTS: Median dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3-14.1), 82.6 (7.8-125.3), 92.3 (13.3-97.3), and 72 (22.8-96.4) µg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (Cmax ) by 8 hours (n = 2). Median time of maximal concentration (Tmax ) for the remaining 5 cats 5.2 (range 4-6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Mean trough serum levetiracetam concentrations were ≥5 µg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate-release levetiracetam for epileptic cats.

Comparison of two melphalan protocols and evaluation of outcome and prognostic factors in multiple myeloma in dogs.

BACKGROUND: Multiple myeloma (MM) in dogs typically is treated with melphalan. A daily melphalan dosing schedule reportedly is well tolerated and associated with favorable outcome. Although anecdotally a pulse dose regimen has resulted in successful responses, little long-term outcome and safety data is available regarding this dosing regimen for dogs with MM. HYPOTHESIS/OBJECTIVES: (1) To compare outcome and adverse event profiles between pulse dose and daily dose melphalan schedules and (2) to report prognostic factors in dogs with MM treated with melphalan. We hypothesized that both protocols would have similar outcomes and tolerability. ANIMALS: Thirty-eight client-owned dogs diagnosed with MM receiving pulse dose (n = 17) or daily dose (n = 21) melphalan. METHODS: Retrospective cohort study assessing outcome and adverse events in dogs receiving either protocol. Risk factors were evaluated for their prognostic relevance. RESULTS: Both regimens were well tolerated and similarly effective, with an overall median survival time of 930 days. Renal disease and neutrophil-to-lymphocyte ratio (NLR) were negative prognostic factors, whereas hypercalcemia and osteolytic lesions were not prognostic factors in this study population. CONCLUSIONS AND CLINICAL IMPORTANCE: Positive results support the use of either dosing regimen for the treatment of dogs with MM, and renal disease and NLR were negative prognostic factors. Prospective, controlled, and randomized studies are warranted to confirm these findings.

Prospective long-term evaluation of parenteral hydroxocobalamin supplementation in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund-Gräsbeck syndrome).

BACKGROUND: Prospective studies on maintenance treatment for Beagles with hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared with serum Cbl concentrations. OBJECTIVES: To evaluate a standardized Cbl supplementation scheme in Beagles with IGS. We hypothesized that a single parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and metabolic remission for up to 2 months. ANIMALS: Six client-owned juvenile Beagles with genetically confirmed IGS and 28 healthy control dogs. METHODS: Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2 months) injections in 5 dogs over a median of 6 months (range, 3-10). Health status was assessed by routine clinical examinations at injection time points and owner observations. Voided urine samples were collected immediately before OH-Cbl injections for measurement of MMA-to-creatinine concentrations using a gas-liquid chromatography-tandem mass spectrometry (GC-MS) method. RESULTS: All dogs were clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation. Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine (median, 2.9). Median urinary MMA concentrations did not differ between dogs with IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections. CONCLUSIONS AND CLINICAL IMPORTANCE: A maintenance parenteral dose of 1 mg OH-Cbl monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic testing.