| Autor: |
Myers PH; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Goulding DR; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Wiltshire RA; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., McGee CA; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Dickerson AB; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Comins MM; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Shi M; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Kissling GE; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Lih FB; Mass Spectrometry Research and Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Deterding LJ; Mass Spectrometry Research and Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Laber-Laird KE; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina., Blankenship-Paris TL; Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina. |
| Abstrakt: |
Buprenorphine, an analgesic commonly used in rodent surgery, requires repeated dosing every 4 to 6 h in order to provide adequate analgesia. However, redosing requires repeated handling, which may itself cause stress. Buprenorphine SR-LAB, which reportedly maintains serum levels of buprenorphine greater than 1 ng/mL for 48 to 72 h, is commercially available. However, the viscosity of the product and small dosing volumes make accurate dosing a challenge. Simbadol is a concentrated formulation of buprenorphine hydrochloride labeled for use in cats with recommended dosing frequency of every 24 h. We measured serum concentrations over time after a single injection of this product in C57BL/6NCrl mice and compared it to standard buprenorphine (Buprenex) and Buprenorphine SR-LAB. Male and female mice were injected subcutaneously with one of the 3 buprenorphine formulations at a dose of 1 mg/kg at time 0. Groups of mice ( n = 8) were euthanized at 1, 4, 8, 12, 16 h for all groups and 24 h for the Simbadol and the Buprenorphine SR-LAB. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine concentrations of buprenorphine in each serum sample. High concentrations were observed in both Simbadol and standard buprenorphine groups one hour after injection (>50 ng/mL). These groups had similar buprenorphine concentration curves, including rates of decline. The standard buprenorphine group had mean concentrations less than 1 ng/mL by 12 h and the Simbadol group by 16 h. In contrast, the Buprenorphine SR-LAB group remained above the 1 ng/mL therapeutic threshold throughout the 24 h. In addition, clinical signs, including increased activity, that lasted for up to an hour after the injection in the Simbadol and standard buprenorphine groups. We conclude that Simbadol does not offer dosing advantages over the standard buprenorphine formulation when given at 1 mg/kg. Buprenorphine SR-LAB maintained a steady concentration of buprenorphine above 1 ng/mL for at least 24 h, and as such is a superior choice for providing long-term analgesia. |
