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.

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.

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.

Ketoprofen pharmacokinetics of R- and S-isomers in juvenile loggerhead sea turtles (Caretta caretta) after single intravenous and single- and multidose intramuscular administration.

Ketoprofen is a nonsteroidal anti-inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX-1 and COX-2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single- and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S-isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once-daily dosing will not require dose adjustment over time. S-isomer pharmacokinetic parameters determined in this study were Cmax of 10.1 µg/ml by IM injection, C0 of 13.4 µg/ml by IV injection, AUC of 44.7 or 69.4 µg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles.

Evaluation of the safety of daily administration of capromorelin in cats.

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin-treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.

Efficacy assessment of an intramammary treatment with a new recrystallized enrofloxacin vs ceftiofur and parenteral enrofloxacin in dairy cows with nonsevere clinical mastitis.

A recrystallized form of enrofloxacin as dehydrate-HCl (enro-C) was assessed for bacteriological and clinical cure efficacies in Holstein-Friesian cows affected of nonsevere clinical mastitis. Treatments were enro-Csusp (n = 81), treated with a pharmaceutical suspension of enro-C/quarter; group enro-Cpd (n = 80) treated as above, but using enro-C powder suspended in water; group CF (n = 65), treated with ceftiofur HCl/quarter; and group enroR (n = 66), treated with standard enrofloxacin solution (5 mg/kg, intramuscular). Cows had a mean milk production of 31 L/day and were 2-3 lactational periods old. Treatments were administered every 24 hr for 3 days. Groups treated with enro-C exhibited statistically significant (p > .05) better clinical cure as compared to groups treated with CF or enroR (95.06%, 96.25%, 67.79%, and 57.55%, for enro-Csusp , enro-Cpd , CF, and enroR , respectively). In contrast, probability of bacteriological cure was not statistically different among treatments. Yet, the outstanding clinical and bacteriological cure rates obtained for enro-C for nonsevere cases of mastitis is superior to previously reported data for parenteral enrofloxacin and other antibacterial-intramammary treatments. Impact of using enro-C on the rate and pattern of bacterial resistance, somatic cell counts and milk electric conductivity, must be studied. Also, the use of enro-C for complicated cases of mastitis should be studied and milk withdrawal times must be accurately established.

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.

Safety evaluation of the interchangeable use of robenacoxib (Onsior™) tablets and solution for injection in dogs.

BACKGROUND: Robenacoxib (Onsior™) is a non-steroidal anti-inflammatory drug developed for canine and feline use for the control of pain and inflammation. It is available as both tablets and solution for injection. The objective of this safety study was to investigate the interchangeable use of two robenacoxib formulations in dogs using a novel study design alternating between oral tablets and subcutaneous injections. Thirty-two naïve healthy 4-month dogs were enrolled in this 88-day study and were randomized among four groups to be untreated or to receive robenacoxib at the highest recommended or elevated dose rates. The dogs were administered three 20-day treatment cycles each separated by a 14-day washout period. Each 20-day cycle was comprised of 10 days of once daily oral administration, 3 days of subcutaneous administration, followed by further 7 days of oral administration (Groups 2 to 4). The control group (Group 1) received oral empty gelatin capsules or subcutaneous saline injections. Assessment of safety was based on general health observations, clinical observations, physical and neurological examinations including ophthalmological examinations, electrocardiographic examinations and clinical pathology evaluations, food and water consumption, body weight, and macroscopic and microscopic examinations. Blood samples were collected for pharmacokinetic evaluation. RESULTS: Blood concentrations of robenacoxib confirmed systemic exposure of all treated dogs. All dogs were in good health through study termination and there were no serious adverse events during the course of the study. No changes in body weight, food consumption, ophthalmic, neurological examinations, electrocardiograms, buccal mucosal blood times, clinical pathology or organ weight were attributable to robenacoxib formulation administration. Primary treatment-related abnormalities were of low incidence at all doses. They were confined to macroscopic and microscopic changes observed locally at the subcutaneous injection sites and microscopic findings within the gastrointestinal tract. These findings were as expected based on previous studies with robenacoxib solution for injection alone and the known properties of this class of compound and mode of administration. There were no adverse effects which could be attributed specifically to the interchangeable use of oral and injectable robenacoxib. CONCLUSIONS: Alternating regimens of robenacoxib tablets and solution for injection were well tolerated in healthy young dogs.

Ovsynch Plus protocol improves ovarian response in anovular Murrah buffaloes in low-breeding season.

The objective of the study was to evaluate the efficacy of ovarian response and pregnancy rate in anovular buffaloes following Ovsynch and Ovsynch Plus protocols. Buffaloes (n = 55) were divided into two groups: Ovsynch group (n = 26): GnRH (10 µg, GnRH1) on Day 0, PGF2 α (25 mg) on Day 7, GnRH (10 µg, GnRH2) on Day 9; Ovsynch Plus group (n = 29): 500 IU equine chorionic gonadotropin (eCG) 72 hr (day -3) prior to Ovsynch protocol, followed by fixed timed artificial insemination (FTAI) 6 and 24 hr after GnRH2 injection in bot groups. Transrectal ultrasonography was performed daily, that is, from day 0 and -3 in Ovsynch and Ovsynch Plus group, respectively for ovarian response and pregnancy diagnosis at day 30 post-insemination. In Ovsynch Plus group, administration of eCG prior to GnRH1 increased (p < .001) the diameter (mm) of dominant follicle (DF) from 10.15 ± 0.26 to 12.23 ± 0.34 within 72 hr of treatment resulting higher ovulatory response to GnRH1. Ovulation after GnRH1 was higher (p < .01) in Ovsynch Plus group (96.6%) than Ovsynch group (61.5%). However, ovulation rate to GnRH2 was similar (p > .05) between groups (Ovsynch group: 76.9% vs. Ovsynch Plus group: 70.0%). Mean DF diameter (mm) that ovulated to both GnRHs was higher (p < .01) than non-ovulated counterparts in both groups (Ovsynch group: 10.80 ± 0.27 vs. 8.47 ± 0.53; Ovsynch Plus group: 11.99 ± 0.24 vs. 9.5 ± 0.63). Pregnancy was established in buffaloes which responded to both GnRHs, irrespective of groups, being higher (p = .52) in Ovsynch Plus group (34.5%) than Ovsynch group (23.1%), though non-significant. In summary, this study showed that eCG inclusion prior to Ovsynch regimen improves ovulatory response in anovular buffaloes during low-breeding season.

Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection.

Suspected aspirin resistance in individual healthy adult warmblood horses.

The reasons for this prospective experimental study were to determine a dosing scheme with loading and maintenance dose of aspirin inducing inhibition of platelet function measured by whole blood impedance aggregometry. Ten horses received aspirin orally in the morning with one loading dose of 4.7-5 mg/kg and maintenance doses of 1-1.3 mg/kg daily the following 4 days. Aggregometries (COLtest, ASPItest, ADPtest) and serum salicylic acid were measured. ASPItest showed significant difference in inhibition at 24 and 48 hr (p < .05) and 96 hr (p < .01). Significant change for ADPtest and COLtest couldn't be detected. Serum salicylic acid concentrations were significantly (p < .01) increased at 6 and 12 hr. Despite this, three horses failed any inhibitory effect of platelet function, suspecting an aspirin resistance. Regarding the other seven horses platelet aggregation induced by ASPItest was reduced between 37% and 100% from baseline at 6 and 12 hr and between 0 and 98% during the next 4 days. Correlations of serum concentration of salicylic acid and aggregometries couldn't be detected. It can be presumed that equine platelets are less susceptible to aspirin what may compromise eventually the anticoagulatory effects and efficacy in preventing and treating diseases with increased platelet activation as endotoxaemia or laminitis.

Pharmacokinetics of firocoxib after intravenous administration of multiple consecutive doses in neonatal foals.

The purpose of this study was to determine the pharmacokinetic profile of intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09 mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for plasma firocoxib analysis using high-performance liquid chromatography with fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4, 6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48, 72 and 96 hr following the final dose. Noncompartmental analysis using the trapezoidal method with linear interpolation revealed a moderate half-life (15.9 ± 9.1 hr) with a large volume of distribution at steady state (1.79 ± 0.57 L/kg) and a clearance (96.0 ± 59.2 ml h-1  kg-1 ) that was more rapid than that observed in adult horses.

Successful treatment of pemphigus foliaceus in a Berrichon du Cher ram with methylprednisolone acetate.

BACKGROUND: Pemphigus foliaceus is a severe, autoimmune blistering skin disease, which is described in humans and some animal species. In small ruminants pemphigus foliaceus has rarely been described and, to the best of the authors' knowledge, little information is available about successful treatment in sheep. AIM: This case report describes a Berrichon du Cher ram with the presumed diagnosis of pemphigus foliaceus. METHODS: The ram was treated with methylprednisolone acetate 40 mg at a dosage of 2.5 mg/kg in one subcuticular injection at four week intervals over a one year period, with regular observation of clinical parameters. Four months after treatment was initiated the haematological parameters showed lymphopenia and leukopenia; some enzyme activities were substantially increased. RESULTS: The ram's dermatological condition improved to the point of complete healing of the affected skin. The ram was discharged in good condition. No adverse effects, except an elevation of some enzymes associated with liver function, were observed. At postmortem examination moderate fatty liver syndrome was the only abnormality found. CONCLUSIONS AND CLINICAL IMPORTANCE: This case report demonstrated that long term therapy with methylprednisolone acetate in a sheep with pemphigus foliaceus did not have a negative effect on clinical parameters. Nevertheless, due to the extended statutory withdrawal period resulting from the regular administration of glucocorticoids, such a therapeutic option must be critically assessed in food producing animals.

Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose.

Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses.

Adverse effects of a 10-day course of ibuprofen in Holstein calves.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for various conditions in cattle. Ibuprofen is an inexpensive short-acting NSAID and is readily available in liquid formulation for administration to bottle-fed calves. We compared the adverse effects of a 10-day course of ibuprofen and placebo in 16 five- to six-week-old Holstein bull calves that were being treated for experimentally induced bovine respiratory syncytial virus infection. Ibuprofen was administered as a liquid in milk replacer at 30 mg/kg divided three times daily. We found an increased prevalence of abomasal ulceration 5 of 8 in the ibuprofen compared to placebo group 2 of 6 (P = NS). There was one (1 of 8) case of mild interstitial nephritis in the ibuprofen and none (0 of 8) in the placebo group (P = NS). Renal function as measured by serum BUN and creatinine levels was not different between groups; no animal demonstrated an increase in creatinine.

Development of a programmable piggyback syringe pump and four-times-a-day injection regimen for superovulation in non-lactating Holstein cows.

The objectives of the present study were to develop a programmable piggyback syringe pump for bovine superovulation and to evaluate the effects of a four-times-a-day injection regimen using the pump. Non-lactating Holstein cows were treated with a total of 30 armour units of porcine FSH by injection four times a day with the pump (study, n = 9) or injection twice a day manually (control, n = 9) for four consecutive days from D10 of the estrous cycle. The pump-driven program successfully induced superovulation in all cows tested. The numbers of small (3- < 5 mm in diameter) and large (≥ 10 mm in diameter) follicles were greater in the study group on D11-13 and D14, respectively. There were fewer unovulated follicles detected on D21 (7 days after estrus) in the study group than in the control group (1.2 ± 0.4 and 3.2 ± 0.6, respectively).

Effects of different five-day progesterone-based synchronization protocols on the estrous response and follicular/luteal dynamics in dairy cows.

This study compared the responses shown by lactating dairy cows to four different P4-based protocols for AI at estrus. Cows with no estrous signs 96 h after progesterone intravaginal device (PRID) removal were subjected to fixed-time AI (FTAI), and their data were also included in the study. In Experiment I, follicular/luteal and endometrial dynamics were assessed every 12 h from the beginning of treatment until AI. The estrous response was examined in Experiment II, and fertility was assessed in both experiments. The protocols consisted of a PRID fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone (GnRH), equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I (40 cows), animals receiving GnRH at the start of treatment showed a significantly higher ovulation rate during the PRID insertion period while estrus was delayed. In Experiment II (351 cows), according to the odds ratios, cows showing luteal activity at the time of treatment were less likely to show estrus than cows with no signs of luteal activity. Treatment affected the estrous response and the interval from PRID removal to estrus but did not affect conception rates 28-34 days post AI. Primiparous cows displayed a better estrous response than multiparous cows. Our findings reveal acceptable results of 5-day P4-based protocols for AI at estrus in high-producing dairy cows. Time from treatment to estrus emerged as a good guide for FTAI after a 5-day P4-based synchronization protocol.

Oral glucocorticoid pulse therapy for induction of treatment of canine pemphigus foliaceus - a comparative study.

BACKGROUND: The management of canine pemphigus foliaceus (PF) often requires long-term immunosuppressive treatment that is often associated with unacceptable adverse effects. High-dose glucocorticoid pulse therapy, an alternative protocole used for pemphigus in people, has been shown to provide rapid improvement in dogs with pemphigus foliaceus and vulgaris. OBJECTIVES: To further identify the benefit of pulse therapy for management of canine PF, we compared the outcomes of oral glucocorticoid pulse and traditional therapies during the first 3 months of disease management. ANIMALS: Dogs were allocated based on their oral glucocorticoid regimen during the first 12 weeks of PF management into the 'traditional' (20 dogs) or the 'pulse' (18 dogs) treatment groups. RESULTS: The proportion of dogs achieving complete remission (CR) during the first 12 weeks of treatment was significantly higher for the 'pulse' (61%) than for the 'traditional' group (15%; P = 0.0063). The maximal oral glucocorticoid dosage given to dogs from the 'traditional' group was significantly higher (median: 3.2 mg/kg) than that given between pulses to dogs from the other group (median: 1.1 mg/kg; P < 0.0001). There was no significant difference between groups in the time needed to achieve CR, the proportion of dogs requiring adjuvant immunosuppressive treatment or in the proportion of dogs experiencing severe adverse drug reactions. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest several benefits associated with oral glucocorticoid pulse therapy, such as a higher proportion of dogs achieving CR during the first 3 months, a lower average maximal oral glucocorticoid dosage given between pulses and minimal adverse drug events.

Pharmacokinetics of a low dose and FDA-labeled dose of diclazuril administered orally as a pelleted topdressing in adult horses.

The purpose of this study was to determine the pharmacokinetics of the FDA-approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (Protazil(TM) , Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collection following the single dose at hour 168, a once daily oral dose was administered for the next 10 days to ensure the drug's concentration reached steady-state. To determine the CSF concentration at steady-state, CSF samples were collected after the 9th oral dose. Blood was then collected after the 10th dose and then at regular intervals up to 168 h. A washout period of 4 weeks was allowed before repeating this protocol for the FDA-labeled dose at 1 mg/kg. Plasma and CSF samples were analyzed by high-pressure liquid chromatography. A one-compartment pharmacokinetic model with first-order oral absorption was fitted to the single administration data. Steady-state pharmacokinetics was performed using noncompartmental analysis for steady-state analysis. The mean (standard deviation) concentration of diclazuril in CSF following the low dose was 26 ng/mL (5 ng/mL), while CSF in the FDA-labeled dose was 25 ng/mL (4 ng/mL), P = 0.3750. Substantial accumulation in plasma occurred at steady-state after the 10th dose for both doses. The results of this study show that diclazuril pellets given at the approved label dose and a lower dose both produce similar plasma drug concentrations at steady-state and attain plasma and CSF concentrations known to inhibit Sarcocystis neurona in cell culture.