Longitudinal evaluation of immunological responses to allergen-specific immunotherapy in horses with IgE associated dermatological disease, a pilot study.

BACKGROUND: The long-term effects of allergen specific immunotherapy (ASIT) on concentrations of circulating immunoglobulin E (IgE) and immunoglobulin G (IgG) in horses have not been reported. OBJECTIVES: To document changes in clinical severity of horses with atopic dermatitis (AD) and to monitor allergen-specific IgE and IgG concentrations during a two-year course of ASIT. ANIMALS: Nineteen client-owned horses with a conditional diagnosis of AD. METHODS AND MATERIALS: Three ASIT groups were randomly assigned based upon results obtained by either intradermal testing (IDT) for regional allergens (n = 7); enzyme-linked immunosorbent assay (ELISA) for specific IgE (n = 6); or a composite of results from both tests (n = 6). Serum concentrations of IgE and IgG specific for allergens included in ASIT were measured at time zero and at four-month intervals. A visual analog scale (VAS) was used to record severity of clinical signs at times zero, 12 and 24 months. RESULTS: Positive correlations were documented between IgE and both immediate and delayed IDT results (P < 0.00001), and between immediate IDT and IgG results (P = 0.003). Specific IgE in sera decreased significantly (P < 0.05) for allergens that were included in ASIT, whereas IgG increased. Across all horses, the mean VAS score decreased by 1.2 units [95% CI: 1.28, 1.14; (P < 0.0001)] during each 12-month period of ASIT therapy. Improvement in clinical signs was noted in 76.5% of the horses following 12 months of ASIT and in 82% after 24 months on ASIT. CONCLUSIONS AND CLINICAL IMPORTANCE: In this pilot study, ASIT in horses with AD provided significant clinical benefit associated with a concomitant reduction of allergen-specific IgE and elevation of IgG.

Effects of powdered whole grapefruit and metoclopramide on the pharmacokinetics of cyclosporine in dogs.

OBJECTIVE: To determine whether oral administration of metoclopramide or a commercially available powdered whole grapefruit (PWG) nutraceutical in combination with cyclosporine enhances systemic availability of cyclosporine in dogs. SAMPLE: 8 healthy mixed-breed dogs in part 1 and 6 of these 8 dogs in part 2. PROCEDURES: Cyclosporine pharmacokinetics were determined over the course of 24 hours after oral administration of cyclosporine (5 mg/kg) alone, cyclosporine with metoclopramide (0.3 to 0.5 mg/kg), cyclosporine with 2 g of PWG, or cyclosporine combined with both metoclopramide and 2 g of PWG by use of a Latin square crossover study with a 14-day washout period between treatments. Sixty days later, 6 of the 8 dogs were given 10 g of PWG followed by cyclosporine, and pharmacokinetic parameters were compared with those previously obtained after administration of cyclosporine alone. RESULTS: Although metoclopramide or coadministration of metoclopramide and 2 g of PWG had no effect on the pharmacokinetic parameters of cyclosporine, compared with results for cyclosporine alone, the higher (10-g) dose of PWG resulted in 29% faster mean time to maximal plasma cyclosporine concentration, 54% larger area under the curve, and 38% lower apparent oral clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Adjustment of the cyclosporine dose may not be needed when metoclopramide is coadministered orally to prevent common adverse effects of cyclosporine. Powdered whole grapefruit has the potential to reduce the required orally administered dose of cyclosporine but only when PWG is used in an amount (at least 10 g) that is currently not cost-effective.