Safety studies of post-surgical buprenorphine therapy for mice

Area of Science:

• Veterinary pharmacology
• Laboratory animal science

Background:

• Concerns regarding adverse events (AE) may lead to suboptimal analgesia in laboratory mice.
• Buprenorphine is a commonly used analgesic, but its safety profile in mice, particularly extended-release formulations, requires thorough investigation.

Purpose of the Study:

• To evaluate the safety and identify potential adverse events (AE) of an extended-release buprenorphine suspension in laboratory mice.
• To determine the maximum tolerated dose and assess the safety of repeated administration in a post-operative setting.

Main Methods:

• Target Animal Safety trials were conducted using BALB/c mice mimicking post-operative conditions.
• Mice received subcutaneous injections of buprenorphine or control suspensions at the intended dose (3.25 mg/kg) and five-fold (5×) excesses (16.25 mg/kg).
• Evaluations included prospective measurements of weight changes, blood chemistry, hematology, and histopathology over various trial durations (4 days, 12 days, 14 months).

Main Results:

• No significant clinical or histopathological findings were observed in mice receiving a single 5× overdose (16.25 mg/kg) over four days.
• In a 12-day repeat-dose study, female mice showed similar clinical and histopathology results between control and buprenorphine groups (total dose 48.75 mg/kg).
• In male mice during the repeat-overdose trial, two out of eight died following the third 16.25 mg/kg overdose, with no cause identified via histopathology. A 14-month study with a single 3.25 mg/kg dose revealed no significant adverse findings.

Conclusions:

• Extended-release buprenorphine suspension demonstrates a high safety tolerance in laboratory mice under appropriate husbandry conditions.
• The findings support the use of this formulation for post-operative analgesia in mice, with careful monitoring recommended during high-dose or repeated administrations.