Extended-release buprenorphine has been extensively used in laboratory animal medicine, yet its onset of analgesia in rats remains largely unexplored. This study aimed to investigate the analgesic onset of 3 different extended-release buprenorphine formulations in rats. Our hypothesis was that the onset of all 3 buprenorphine formulations are comparable and are detectable as early as 5 minutes after administration in rats. Sprague-Dawley rats (both male and female, n = 40) were randomly assigned to 4 treatment groups: (1) saline (1 mL/0.1 kg SC, once); (2) Bup-ER (1.2 mg/kg SC, once); (3) Ethiqa-XR (0.65 mg/kg SC, once); and (4) LAT-Bup (Zorbium, 10 mg/kg transdermal, once). Thermal sensitivity (using a hot plate test) was assessed at time points of 5, 15, 30, 45, 60, 120, 180, and 240 minutes following drug administration. Results were as follows: (1) compared with the saline group, Bup-ER's thermal latency significantly increased at 45 (11.05 ± 1.13), 60 (12.5 ± 1.16), 120 (13.7 ± 1.24), 180 (12.48 ± 0.81), and 240 (11.64 ± 0.7) minutes; (2) Ethiqa-XR's thermal latency significantly increased at 180 (12.01 ± 0.6) and 240 (11.76 ± 0.81) minutes; and (3) LAT-Bup's thermal latency significantly increased at 120 (11.27 ± 1.16), 180 (13.97 ± 1.35), and 240 (14.8 ± 1.26) minutes. There were no differences between sexes. LAT-Bup and Bup-ER provided buprenorphine plasma levels exceeding the purported therapeutic threshold of 1 ng/mL by 5 minutes, while Ethiqa-XR exceeded the threshold at 45 minutes. We concluded that these 3 buprenorphine extended-release formulations did not exhibit a time to onset of analgesia within 5 minutes. This study demonstrates that despite all 3 extended-release formulations reaching a purported plasma therapeutic threshold earlier, the clinical onset of analgesia for the hot plate test was shortest for Bup-ER (45 minutes), followed by LAT-Bup (120 minutes) and Ethiqa-XR (180 minutes) in Sprague-Dawley rats.
Alamaw et al. (2026) studied this question.