A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with\nincreasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65mg/kg afforded\nclinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold\nexcess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and\nunderlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses\nof 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing.\nThese results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in\nlaboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug\ntherapy.
Loading....