Pharmacokinetics of esomeprazole following intravenous and oral administration in healthy dogs.

Investigation into the pharmacokinetic profile of esomeprazole was conducted using eight healthy dogs after intravenous (IV) and oral (po) administration in a two-part randomized crossover study. The dogs were fasted for a minimum of 12 hours and then received esomeprazole either intravenously (dose range 0.93-1.48 mg/kg) or orally using an enteric-coated formulation (dose range 0.95-1.50 mg/kg). After a 1-week washout period, the dogs received an alternative treatment. Serial blood samples were collected at predetermined time points, and plasma esomeprazole concentrations were determined by using ultra-high-performance liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Then, the area under the plasma concentration/time curve (AUC) and maximal plasma concentration (Cmax) values were normalized to a 1.0 mg/kg dose of esomeprazole, that is, AUC/dose. Median (range) dose-normalized peak plasma concentration (Cmax) values for the IV and po formulations were 4.06 µg/mL (2.47-4.57 µg/mL) and 1.04 µg/mL (0.31-1.91 µg/mL), respectively. The median (range) time-to-peak concentration (Tmax) for the po formulation was 105 minutes (45-360 minutes). Median (range) plasma terminal half-life (t½) was 45.56 minutes (39.43-64.20 minutes) for the IV formulation and 63.97 minutes (44.02-109.94 minutes) for the enteric-coated po formulation. The median (range) po bioavailability was 63.33% (32.26%-79.77%). Clinically, both po and IV formulations were well tolerated with minimal side effects observed.

Comparison of the effects of enteral psyllium, magnesium sulphate and their combination for removal of sand from the large colon of horses.

Prospective studies documenting the efficacy and side effects of medical treatment for colonic sand accumulation in horses are limited. The purpose of the study was to compare the effect of enteral administration of magnesium sulphate (MgSO4), psyllium mucilloid (psyllium), and a combination of MgSO4 and psyllium on the evacuation of large accumulations of sand in the large colon of adult horses. Thirty-four horses with naturally acquired, large sand accumulations (>5 cm × 15 cm) identified on abdominal radiography were randomly allocated to one of three treatment groups: (1) 1 g/kg psyllium (n = 12); (2) 1 g/kg MgSO4 (n = 10), or (3) their combination (n = 12). Treatments were administered once a day via nasogastric intubation and continued for a total of 4 days. Lateral radiographs of the ventral abdomen were repeated on day 4 of treatment. If the area of sand in the radiographic image was <25 cm(2) on day 4, the sand accumulation was considered resolved. Of 12 horses treated with a combination of psyllium and MgSO4, nine evacuated the sand from the ventral colon within 4 days. In comparison, only 3/12 horses treated with psyllium and 2/10 horses treated with MgSO4 resolved (both significantly different from the combination; P <0.05). Large accumulations of sand in the large colon of horses can be treated medically. Administering a combination of psyllium and MgSO4 via nasogastric intubation once daily for a total of 4 days was a more effective treatment than either constituent alone.

Administration of trimethoprim-sulphadimidine does not improve healing of glandular gastric ulceration in horses receiving omeprazole: a randomised, blinded, clinical study.

BACKGROUND: Interest in Equine Gastric Ulcer Syndrome (EGUS) has recently increased in part due to a growing awareness of the differences between squamous and glandular disease. The pathophysiology and epidemiology of squamous and glandular disease are different and recently it has been shown that the response of glandular gastric ulceration to monotherapy with omeprazole is poor. Given these differences it has been recommended that specific treatment guidelines be formulated for equine glandular disease and that adjunctive therapies be investigated. Along these lines it has been suggested that the addition of antimicrobials may enhance healing. The objective of this study was to investigate whether the addition of trimethoprim-sulphadimidine to omeprazole therapy would result in superior healing of naturally occurring equine glandular ulceration compared with omeprazole monotherapy. RESULTS: Combination therapy of omeprazole plus trimethoprim-sulphadimidine could not be demonstrated to be superior to omeprazole monotherapy. Healing of the glandular mucosa was observed in 7/15 (47%; 95% CI 24 to 71%) and 3/13 (23%; 95% CI 7% to 50%) of horses in the TMPS and OMEP groups, respectively (OR = 1.8; 95% CI 0.32 to 10.0; p = 0.67). Improvement of the glandular mucosa was observed in 12/15 (80%; 95% CI 56 to 94%) and 9/13 (69%; 95% CI 42 to 89%) of horses in the TMPS and OMEP groups, respectively (OR = 2.9; 95% CI 0.6 to 15.0; p = 0.25). CONCLUSIONS: The results of the present study do not support the addition of trimethoprim-sulphadimidine to therapeutic protocols for equine glandular ulceration. Several limitations were present in the study and the use of antimicrobials as an adjunctive treatment warrants further investigation. However, given the potential deleterious consequences associated with the indiscriminate use of antimicrobials, the inclusion of antimicrobials in treatment regimes for EGUS is not justified until their efficacy is further validated.