Safety of spironolactone in dogs with chronic heart failure because of degenerative valvular disease: a population-based, longitudinal study.

BACKGROUND: Spironolactone treatment in humans is associated with an increased risk of hyperkalemia and renal dysfunction. HYPOTHESIS: Dogs with cardiac disease treated with spironolactone, in addition to conventional therapy, are not at higher risk for adverse events (AEs) than those receiving solely conventional therapy. ANIMALS: One hundred and ninety-six client-owned dogs with naturally occurring myxomatous mitral valve disease. METHODS: Prospective, double-blinded field study with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin-converting enzyme inhibitor, plus furosemide and digoxin if needed). Safety was compared between treatment groups, using the frequency of AEs, death caused by cardiac disease, renal disease, or both, and variations in serum sodium, potassium, urea, and creatinine concentrations. For the latter, population-specific reference intervals were established and out of range values (ORV) analyzed. RESULTS: The number of AEs was similar in the spironolactone and reference groups (188 and 208, respectively), when followed for median duration of 217 days (range [2-1,333]). At each study time point, the percentage of dogs showing ORV was similar between groups. There were a higher number of deaths because of cardiac disease, renal disease or both in the reference group (30.7% versus 13.7%) (P = .0043). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with heart failure receiving spironolactone in addition to conventional treatment are not at a higher risk for AEs, death caused by cardiac disease, renal disease, or both, hyperkalemia, or azotemia.

Efficacy of permethrin, dinotefuran and pyriproxyfen on adult fleas, flea eggs collection, and flea egg development following transplantation of mature female fleas (Ctenocephalides felis felis) from cats to dogs.

A novel spot-on formulation combining permethrin, pyriproxifen and dinotefuran (Vectra 3D™ spot-on solution for dogs) was evaluated in adult Beagle dogs in a study to determine adulticidal efficacy, egg laying inhibition and viability of Ctenocephalides felis felis eggs (development and emergence of fleas from the collected eggs). Prior to treatment sixteen dogs were checked for their ability to keep fleas 24 hours after infestation and were allocated to treatment groups: 8 dogs served as untreated controls, and 8 dogs were treated once with the tested formulation. The spot on was administered respecting the laboratory recommendations at a dosage of 65-126 mg/kg of permethrin; 8.9-17.4 mg/kg of dinotefuran and 0.8-1.5mg/kg of pyriproxyfen. Each dog was infested with 100 adult cat fleas ready to lay eggs after 72 hours spent feeding on cats. Dogs were infested 24 hours after treatment and then weekly during 63 days. Eggs were collected and counted 24 hours after each infestation and dogs were combed 48 hours after each infestation. Fleas were counted and removed. Collected eggs were placed in incubator to study their development in larvae and into newly emerged adults. A single treatment provided 99.7% adulticidal efficacy on fleas within 48 hours after treatment and controlled re-infestations for up to 30 days (efficacy >96.20%, p<0.05). The egg laying inhibition was over 92.3% for up to 29 days (p<0.05). The adult emergence inhibition remained 100% during 8 weeks after treatment and was 99.8% nine weeks after treatment (p<0.001).

Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease.

BACKGROUND: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. HYPOTHESIS: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). ANIMALS: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). METHODS: Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR. RESULTS: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22-0.90; log rank test, P = .017). Risk of cardiac-related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13-0.76; P = .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). CONCLUSION AND CLINICAL IMPORTANCE: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.

Determination of a dosage regimen of colistin by pharmacokinetic/pharmacodynamic integration and modeling for treatment of G.I.T. disease in pigs.

Colistin is an antimicrobial drug of the polymyxin group and COLIVET SOLUTION is an aqueous solution containing colistin sulphate (2 x 10(6) IU/mL), formulated for oral administration. The target species is the pig, particularly the suckling and post weaning animal. This investigation was undertaken to provide pharmacokinetic and pharmacodynamic data on which to base the selection of dosage rate and interval of the solution for the treatment of porcine colibacillosis. Colistin absorption from the gastrointestinal tract of young pigs, when administered at dosage rates of 25,000, 50,000 and 100,000 IU/kg, was slight or absent. The drug was therefore restricted almost entirely to the required site of action. The colistin concentration-time profile within the jejunum and ileum was established, and this enabled determination of the pharmacokinetic variables, maximum concentration (C(max)) and area under curve (AUC) and derivation of the surrogate indices of antibacterial activity, C(max)/minimum inhibitory concentration (MIC) and AUC/MIC through integration of in vivo data with the results of in vitro potency studies for four strains of Escherichia coli. In the in vitro bacterial growth inhibition studies colistin acted by a concentration-dependent killing mechanism. Numerical values for the surrogate parameter AUC/MIC producing bactericidal and eradication effects of colistin against four strains of E. coli were established by PK-PD modeling based on the sigmoidal E(max) equation. These data were used to predict a daily dosage regimen for colistin.