ABSTRACT
OBJECTIVES: To determine the potency and reproducibility of milbemycin oxime when compounded as an aqueous suspension (20 mg/mL). MATERIALS AND METHODS: Preparation choice reflected current prescribing practices. Samples were acquired by prescription from two national veterinary compounding pharmacies at three time points. Two different storage conditions were evaluated and sampled at four time points from the order date (day 7, 14, 21 and 28). Milbemycin oxime recovery was performed by solid-phase extraction and concentration strength measured via high-performance liquid chromatography. RESULTS: The average concentration on day 7 for Pharmacy A samples was 16.29 mg/mL [confidence interval (CI): 15.66 to 16.92] with a coefficient of variation (CV) = 11%, while for Pharmacy B it was 20.46 mg/mL (CI: 19.83 to 21.08) with CV = 22%. The mean decrease in concentration over 28 days for Pharmacy A was 22% (CI: 9% to 34%) while Pharmacy B was 18% (CI: 2% to 35%). CLINICAL SIGNIFICANCE: The compounded milbemycin oxime suspensions evaluated in this study deviated by more than 10% from their labelled strength in five of the six lots. Clinical efficacy of compounded milbemycin oxime suspensions remains unknown and the use of these products should be discouraged at this time.
Subject(s)
Drug Compounding/veterinary , Macrolides , Administration, Oral , Animals , Macrolides/analysis , Prescription Drugs/analysis , Reproducibility of ResultsABSTRACT
Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.