Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Rats

• Published in: Journal of the American Association for Laboratory Animal Science Vol. 60; no. 6; pp. 667 - 674
• Main Authors: Houston, Elizabeth R, Tan, Sarah M, Thomas, Samantha M, Stasula, Ulana L, Burton, Mollie K, Knych, Heather K, Kendall, Lon V
• Format: Journal Article
• Language: English
• Published: United States American Association for Laboratory Animal Science 01-11-2021
• Subjects: Analgesics, Opioid - therapeutic use; Animals; Buprenorphine - therapeutic use; Cats; Delayed-Action Preparations; Female; Male; Original Research; Pain - drug therapy; Pain Measurement; Rats
• ISSN: 1559-6109
• DOI: 10.30802/AALAS-JAALAS-21-000055

Buprenorphine (Bup) is an opioid analgesic that is commonly used in laboratory rodents to provide postoperative analgesia. However, dosing every 4 to 6 h is necessary to maintain an analgesic plasma concentration of the drug. A long lasting,highly concentrated veterinary formulation of Bup (LHC-Bup) has been used to provide prolonged analgesia in cats and nonhuman primates. In the current study, we evaluated the duration of efficacy of LHC-Bup to determine if this formulation would provide a similarly prolonged analgesia in rats. Drug concentrations were measured after subcutaneous injectionof 0.5 mg/kg LHC-Bup in both male and female rats. Plasma levels were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and72 h. Male and female rats had peak plasma levels of LHC-Bup at 90 ng/and 34 ng/mL, respectively, at 15 min after administration, with a steady decrease by 24 h to 0.7 ng/mL in males and 1.3 ng/mL in females. Mechanical pain tolerance wasevaluated after LHC-Bup administration using a Randall-Selitto analgesiometer to assess paw withdrawal. Male rats had a significantly longer paw withdrawal time for up to 12 h after administration, and females had longer paw withdrawal timesfor up to 24 h. An experimental laparotomy model was then used to assess the clinical efficacy of LHC-Bup at 0.5 mg/kg. LHC-Bup treatment was associated with a greater total distance traveled, reduced time to retrieve a food treat, and reduced grooming from 3 to 12 h after surgery as compared with saline controls. Groups receiving LHC-Bup showed coprophagy whereas other rats did not. These results suggest that administering LHC-Bup at 0.5 mg/kg provides therapeutic plasma concentrations for 12 to 24 h after administration and analgesic efficacy for at least 12 h after dosing. As such, LHC-Bup is a suitable alternative to Bup-HCl.