RT Journal Article
SR Electronic
T1 Pharmacokinetics of Sustained-release Buprenorphine and Extended-release Buprenorphine in Mice with Surgical Catheterization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.14.484329
DO 10.1101/2022.03.14.484329
A1 Saenz, Marissa
A1 Bloom-Saldana, Elizabeth
A1 Synold, Tim
A1 Ermel, Richard W
A1 Fueger, Patrick T
A1 Finlay, James B
YR 2022
UL http://biorxiv.org/content/early/2022/03/17/2022.03.14.484329.abstract
AB The Guide for the Care and Use of Laboratory Animals strongly encourages the use of pharmaceutical grade chemicals and analgesics. The extra-label use of sustained-release buprenorphine (SRB) is commonly administered to rodents to mitigate moderate-to-severe pain. An FDA-indexed buprenorphine formulation, known as extended-release buprenorphine (XRB), has recently become available and is currently the only pharmaceutical grade slow-release buprenorphine approved for use in mice and rats. However, no studies have directly compared the pharmacokinetic (PK) parameters and therapeutic efficacy of SRB and XRB in surgically catheterized mice. Thus, we compared the plasma buprenorphine concentrations and PK parameters of SRB and XRB in mice after surgical catheterization. We hypothesized that mice treated with SRB or XRB would have circulating buprenorphine concentrations exceeding the therapeutic threshold for up to 72-hours post-operatively. Male and female C57Bl/6J mice were anesthetized, treated with either SRB (1 mg/kg, SC, once) or XRB (3.25 mg/kg, SC, once) and underwent surgical catheterization. At 6, 24, 48, and 72 h after SRB or XRB administration, arterial blood samples were collected. Post-operative weight loss was similar between groups with a decline of 11.7 ± 1.6 and 12.3 ± 0.7% in males and 7.6 ± 2.2 and 8.1 ± 1.1% (mean ± SEM) in females treated with SRB and XRB, respectively. Both SRB and XRB maintained circulating buprenorphine concentrations above the therapeutic level of 1.0 ng/mL for 72 h after administration. XRB buprenorphine concentrations were significantly greater (3-4-fold) than SRB concentrations at 6, 24, and 48 h, commensurate with the increase dose concentration of XRB to SRB. These results support the use of either SRB or XRB for the alleviation of postoperative pain in mice. The new availability of FDA-indexed XRB increases the options for safe and effective pharmaceutical grade analgesia in rodents.Competing Interest StatementThe authors have declared no competing interest.SRBsustained-release buprenorphineXRBextended-release buprenorphineMASAmouse antenna for sampling accessNCAnon-compartmental analysis