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  • Title: Comparative Pharmacokinetics and Injection Site Histopathology in Nude Mice Treated with Long-acting Buprenorphine Formulations.
    Author: Illario JA, Osborn KG, Garcia AV, Sepulveda YJ, Momper JD, Kiel JW, Kirihennedige AS, Sun SA, Richter PJ.
    Journal: J Am Assoc Lab Anim Sci; 2023 Mar 01; 62(2):147-152. PubMed ID: 36813268.
    Abstract:
    Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of either drug would provide and sustain the purported therapeutic plasma concentration of buprenorphine (1 ng/mL) over 72 h in nude mice and to characterize the injection site histopathology. NU/NU nude and NU/+ heterozygous mice were subcutaneously injected with extended-release buprenorphine polymeric formulation (ER; 1 mg/kg), extendedrelease buprenorphine suspension (XR; 3.25 mg/kg), or saline (2.5 mL/kg). Plasma concentrations of buprenorphine were measured 6, 24, 48, and 72 h after injection. The injection site was examined histologically at 96 h after administration. XR dosing yielded significantly higher plasma buprenorphine concentrations than did ER dosing at every time point in both nude and heterozygous mice. No significant difference in plasma buprenorphine concentrations were detected between nude and heterozygous mice. Both formulations yielded plasma levels of buprenorphine of over 1 ng/mL at 6 h; XR sustained buprenorphine plasma levels above 1 ng/mL for over 48 h, whereas ER sustained this level for over 6 h. Injections sites of both formulations were characterized by a cystic lesion with a fibrous/fibroblastic capsule. ER induced more inflammatory infiltrates than did XR. This study indicates that while both XR and ER are suitable for use in nude mice, XR has a longer duration of likely therapeutic plasma levels and induces less subcutaneous inflammation at the injection site.
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