Efficacy and Pharmacokinetics of 3 Sustained-Release Buprenorphine Formulations in Cairo Spiny Mice (Acomys cahirinus)

3种缓释丁丙诺啡制剂在开罗棘鼠(Acomys cahirinus)中的疗效和药代动力学研究

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Abstract

African spiny mice (Acomys spp.) are an emerging animal model for regeneration due to their remarkable healing capabilities. Defining characteristics of these species include fragile skin that sloughs easily and shedding of the tail skin when grabbed, making handling and administration of parenteral drugs difficult in conscious animals. In addition, many studies in spiny mice involve painful procedures. To our knowledge, there are no reports regarding analgesia in Acomys spp. This prospective study aimed to assess 3 sustained-release buprenorphine formulations-lipid-bound extended-release buprenorphine (XRB), polymeric sustained-release buprenorphine (SRB), and long-acting transdermal buprenorphine (TB)-in spiny mice. Adult male and female Cairo spiny mice (Acomys cahirinus) were included and administered 1 of the 3 treatments (XRB 3.25 mg/kg, SRB 1 mg/kg, or TB 20 mg/kg). Tail flick assays to assess nociception and terminal blood collection for pharmacokinetic analysis were performed at baseline and a set timepoint following treatment administration (1, 2, 4, 8, 24, 48, and 72 hours) (n = 3 of each sex per timepoint per treatment group). Additional animals underwent repeated serial tail flick assays at 1, 2, 4, 8, 24, 48, and 72 hours following the administration of treatment or sterile saline (n = 5-8 of each sex per treatment group). XRB displayed the longest duration at which mean plasma buprenorphine concentrations were >1 ng/mL, with the drug remaining above this level for 48-72 hours, compared with 24-48 hours in spiny mice receiving TB and 8 hours in those receiving SRB. On serial tail flick assays, the mean percentage of maximum possible efficacy was highest at all timepoints up to 72 hours in the TB group, followed by the XRB group, suggestive of greater analgesic efficacy. Several spiny mice receiving SRB developed ulcerative skin lesions within 24 hours of administration, so this treatment is not recommended in Acomys without additional evaluation. XRB and TB are promising analgesic therapies in spiny mice, and treatment selection should be based on whether duration of action or ease of application is the priority.

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