Efficacy of oclacitinib (Apoquel®) compared with prednisolone for the control of pruritus and clinical signs associated with allergic dermatitis in client-owned dogs in Australia.

BACKGROUND: Oral glucocorticoids are widely used to reduce pruritus and dermatitis associated with allergic dermatitis. Data suggest that oclacitinib, a Janus kinase inhibitor, is a safe and effective alternative. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy and safety of oclacitinib compared with prednisolone for the control of pruritus associated with allergic dermatitis in a single-masked, controlled clinical trial with a randomized complete block design. ANIMALS: Client-owned dogs (n = 123) with a presumptive diagnosis of allergic dermatitis and moderate to severe pruritus as assessed by the pet owner were enrolled. METHODS: Dogs were randomized to treatment with either oclacitinib (0.4-0.6 mg/kg orally twice daily for 14 days, then once daily) or prednisolone (0.5-1.0 mg/kg once daily for 6 days, then every other day) for 28 days. An enhanced visual analog scale (VAS) was used by owners to assess pruritus and by veterinarians to assess dermatitis, at all time points assessed. RESULTS: Both treatments produced a rapid onset of efficacy within 4 h. The mean reductions in pruritus and dermatitis scores were not significantly different between the treatments except on day 14, when reductions were more pronounced for oclacitinib than prednisolone (P = 0.0193 for owner pruritus scores; P = 0.0252 for veterinarian dermatitis scores). Adverse events were reported with similar frequency in both groups. CONCLUSION AND CLINICAL IMPORTANCE: In this study, both oclacitinib and prednisolone provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with substantial improvement in pruritus, reported by owners, and dermatitis, reported by veterinarians.

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs.

OBJECTIVE: To compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs. STUDY DESIGN: Prospective, randomized. experimental study. ANIMALS: Six female, neutered Beagle dogs (13.3±1.0 kg), aged 3.6±0.1 years. METHODS: Anaesthesia was induced with propofol (8.3±1.1 mg kg(-1)) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO(2))=40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg(-1) (M); ropivacaine 0.75% 1.65 mg kg(-1) (R) or methadone 1% 0.1 mg kg(-1) + ropivacaine 0.75% 1.65 mg kg(-1) (RM) in equal volumes (0.23 mL kg(-1)) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0). RESULTS: Mean overall heart rate (HR in beats minute(-1)) was significantly lower after treatment M (119±16) (p=0.0019), R (110±18) (p< 0.0001) and RM (109±13) (p<0.0001), compared to treatment P (135±21). Additionally, a significant difference in HR between treatments RM and M was found (p=0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO(2)). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO(2) . A transient unilateral Horner's syndrome occurred in one dog after treatment R. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.

Influence of a preload of hydroxyethylstarch 6% on the cardiovascular effects of epidural administration of ropivacaine 0.75% in anaesthetized dogs.

OBJECTIVE: To evaluate the cardiovascular effects of a preload of hydroxyethylstarch 6% (HES), preceding an epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs. ANIMALS: Six female, neutered Beagle dogs (mean 13.3 ± SD 1.0 kg; 3.6 ± 0.1 years). STUDY DESIGN: Randomized experimental cross-over study (washout of 1 month). METHODS: Anaesthesia was induced with propofol and maintained with isoflurane in oxygen/air. All dogs were anaesthetized twice to receive either treatment HESR (continuous rate infusion [CRI] of 7 mL kg(-1) HES started 30 minutes [T-30] prior to epidural administration of ropivacaine 0.75% 1.65 mg kg(-1) at T0) or treatment R (no HES preload and similar dose and timing of epidural ropivacaine administration). Baseline measurements were obtained at T-5. Heart rate (HR), mean (MAP), diastolic (DAP) and systolic (SAP) invasive arterial pressures, cardiac output (Lithium dilution and pulse contour analysis) and derived parameters were recorded every 5 minutes for 60 minutes. Statistical analysis was performed on five dogs, due to the death of one dog. RESULTS: Clinically relevant decreases in MAP (<60 mmHg) were observed for 20 and 40 minutes following epidural administration in treatments HESR and R respectively. Significant decreases in MAP and DAP were present after treatment HESR for up to 20 minutes following epidural administration. No significant within-treatment and overall differences were observed for other cardiovascular parameters. A transient unilateral Horner's syndrome occurred in two dogs (one in each treatment). One dog died after severe hypotension, associated with epidural anaesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of 7 mL kg(-1) HES administered over 30 minutes before epidural treatment did not prevent hypotension induced by epidural ropivacaine 0.75%. Epidural administration of ropivacaine 0.75% in isoflurane anaesthetized dogs was associated with a high incidence of adverse effects in this study.

Idiopathic sterile inflammation of the epidural fat and epaxial muscles causing paraplegia in a mixed-breed dog.

CASE DESCRIPTION: A 4-year-old sexually intact male mixed-breed dog was evaluated because of clinical signs of acute-onset pelvic limb ataxia, rapidly progressing to paraplegia with severe spinal hyperesthesia. CLINICAL FINDINGS: General physical examination revealed pyrexia, tachycardia, and tachypnea. Neurologic examination demonstrated severe spinal hyperesthesia and paraplegia with decreased nociception. Magnetic resonance imaging revealed extradural spinal cord compression at T13-L1 and hyperintense lesions on T1- and T2-weighted images in the epaxial musculature and epidural space. TREATMENT AND OUTCOME: Decompressive surgery, consisting of a continuous dorsal laminectomy, with copious lavage of the vertebral canal was performed. Cultures of blood, urine, and surgical site samples were negative. Histologic examination results for samples obtained during surgery demonstrated suppurative myositis and steatitis. These findings confirmed a diagnosis of sterile idiopathic inflammation of the epidural fat and epaxial muscles with spinal cord compression. The dog's neurologic status started to improve 1 week after surgery. After surgery, the dog received supportive care including antimicrobials and NSAIDs. The dog was ambulatory 1 month after surgery and was fully ambulatory despite signs of mild bilateral pelvic limb ataxia 3 years after surgery. CLINICAL RELEVANCE: Although idiopathic sterile inflammation of adipose tissue, referred to as panniculitis, more commonly affects subcutaneous tissue, its presence in the vertebral canal is rare. Specific MRI findings described in this report may help in reaching a presumptive diagnosis of this neurologic disorder. A definitive diagnosis and successful long-term outcome in affected patients can be achieved by decompressive surgery and histologic examination of surgical biopsy samples.

Influence of P-glycoprotein modulation on plasma concentrations and pharmacokinetics of orally administered prednisolone in dogs.

OBJECTIVE: To evaluate the impact of modulation of the membrane-bound efflux pump P-glycoprotein (P-gp) on plasma concentrations of orally administered prednisolone in dogs. ANIMALS: 7 healthy adult Beagles. PROCEDURES: Each dog received 3 treatments (control [no treatment], rifampicin [100 mg/d, PO, for 21 days, as an inducer of P-gp], and ketoconazole [100 mg/d, PO, for 21 days, as an inhibitor of P-gp]). A single dose of prednisolone (1 mg/kg, PO) was administered on day 8 of each treatment period. There was a 7-day washout period between subsequent treatments. Plasma concentrations of prednisolone were determined by use of a validated liquid chromatography-tandem mass spectrometry method. Duodenum and colon biopsy specimens were obtained endoscopically from anesthetized dogs and assessed for P-gp protein labeling via immunohistochemical analysis and mRNA quantification via real-time PCR assay. Total fecal collection was performed for evaluation of effects of P-gp modulation on digestion of nutrients. RESULTS: Rifampicin treatment upregulated duodenal P-gp in dogs and significantly reduced the area under the plasma concentration-time curve of prednisolone. Ketoconazole typically downregulated expression of duodenal P-gp, with a subsequent increase in the area under the plasma concentration-time curve of prednisolone. There was a noticeable interindividual difference in response. Digestion of nutrients was not affected. CONCLUSIONS AND CLINICAL RELEVANCE: Modulation of P-gp expression influenced plasma concentrations of prednisolone after oral administration in dogs. Thus, treatment response to prednisolone may be influenced by coadministration of P-gp-modulating medications or feed ingredients.