A Long-Term Study of a Lipid-Buprenorphine Implant in Rats

Animal models to study opiates are of growing interest. We have examined the short-term safety of buprenorphine implants in Fischer F344/NTac rats treated with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Here we report the results of a long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14-month evaluation showed no abnormal findings that could be attributed to the drug or lipid suspension. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery in laboratory animals and suggest that this model may be used to study long-term effects of opiate therapy.