Use of mirtazapine in the treatment of canine behaviour problems: A review of 32 cases.

BACKGROUND: Canine behaviour problems seen by speciality behavioural medicine services often involve chronic anxiety disorders that have resulted in maladaptation of the individual to its environment. Common stressors include the presence of other individuals (other dogs or people), noise and being alone. The treatment of these behavioural problems usually includes a combination of behaviour modification, environmental modification and biological therapies. Within the latter, anxiolytic drugs such as clomipramine or fluoxetine have proven useful. METHODS: Here, we present a retrospectively analysed series of 32 cases that were treated with the anxiolytic drug mirtazapine, which is widely used in human medicine but has not previously been reported for the treatment of behavioural problems in dogs (although it is marketed as an appetite stimulant in cats). Cases included dogs with a range of anxiety-related behavioural problems. RESULTS: Eighty-one percent of dogs that presented with a behavioural problem showed improvement and suspected adverse effects were mild and tolerable. LIMITATIONS: Further studies are required to isolate this result from the other therapeutic measures and to compare its efficacy with other drugs. CONCLUSION: Mirtazapine appears to be a suitable and safe option for the treatment of anxiety-related behavioural problems in dogs.

Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System.

AIM: The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes. METHODS: We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products. RESULTS: Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3. CONCLUSIONS: Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for C(max) or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies.

Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer.

PURPOSE: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. MATERIALS AND METHODS: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high pressure liquid chromatography assay. RESULTS: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 microg/ml and the mean last AUC was 158 microg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. CONCLUSIONS: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.