Serum Buprenorphine Concentrations and Behavioral Activity in Mice After a Single Subcutaneous Injection of Simbadol, Buprenorphine SR-LAB, or Standard Buprenorphine

Abstract

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.

Post-Injury Buprenorphine Administration Is Associated with Long-Term Region-Specific Glial Alterations in Rats

“…As sustained release Bup works to reduce pain for days [ 19 , 74 ] and alterations in opioid signaling in astrocytes alters mechanical sensitivity [ 66 ], the WNT was performed to investigate potential Bup-SR-Lab-associated changes in somatosensory sensitivity 4w following cFPI or sham injury. In agreement with previous studies from both our and other groups [ 24 , 28 , 30 , 31 ], animals sustaining cFPI displayed hypersensitivity and agitation to the stimulation as compared with animals sustaining sham injury at 4w post-injury.…”

Pharmacokinetics of Extended-release Buprenorphine (Ethiqa) in Female Yorkshire Swine (Sus scrofa domestica)

“…XRB (Ethiqa) is currently the only pharmaceutical grade FDA-indexed extended-release buprenorphine formulation that is approved for use in mice and rats. 29,57 In multiple strains of mice and rats, pharmacokinetic studies revealed a single injection of XRB (Ethiqa) provides therapeutic plasma concentrations for 48-72 h. 1,4,21,22,23,26,31,32,40 Additionally, XRB (Ethiqa) has a superior safety profile and long-lasting analgesia effects of up-to 72 h in mice and rats after a single subcutaneous injection. 3,7,16,19,24,40,48 Our results indicate in swine XRB (Ethiqa) provides longer therapeutic buprenorphine concentrations, consistent with what is observed in other non-rodent species and swine breeds.…”

Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

“…As sustained release Bup works to reduce analgesia for days 19,75 and alterations in opioid signaling in astrocytes alters mechanical sensitivity 67 , the WNT was performed to investigate potential Bup-SR-Labassociated changes in somatosensory sensitivity 4w following cFPI or sham injury. In agreement with previous studies from both our and other groups 24,28,30,31 , animals sustaining cFPI displayed hypersensitivity and agitation to the stimulation as compared with animals sustaining sham injury at 4w post-injury.…”