Lack of absorption of a sustained-release buprenorphine formulation administered subcutaneously to athymic nude rats

C. Douglas Page, Rachel Sarabia-Estrada, R. Jay Hoffman, Chih Ping Lo, Naomi M. Gades

Research output: Contribution to journalArticle

Abstract

Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.

Original languageEnglish (US)
Pages (from-to)597-600
Number of pages4
JournalJournal of the American Association for Laboratory Animal Science
Volume58
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

buprenorphine
rats
plasma cells
skin (animal)
lymphocytes
Institutional Animal Care and Use Committee
xenotransplantation
Rattus norvegicus
nonsteroidal anti-inflammatory agents
spine (bones)
analgesics
shoulders
blood vessels
spinal cord
metastasis
connective tissues
cell-mediated immunity
histopathology
breast neoplasms
liquid chromatography

ASJC Scopus subject areas

  • Animal Science and Zoology

Cite this

Lack of absorption of a sustained-release buprenorphine formulation administered subcutaneously to athymic nude rats. / Douglas Page, C.; Sarabia-Estrada, Rachel; Jay Hoffman, R.; Lo, Chih Ping; Gades, Naomi M.

In: Journal of the American Association for Laboratory Animal Science, Vol. 58, No. 5, 01.01.2019, p. 597-600.

Research output: Contribution to journalArticle

@article{18e17925ebf94a328c40dfedd60da458,
title = "Lack of absorption of a sustained-release buprenorphine formulation administered subcutaneously to athymic nude rats",
abstract = "Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.",
author = "{Douglas Page}, C. and Rachel Sarabia-Estrada and {Jay Hoffman}, R. and Lo, {Chih Ping} and Gades, {Naomi M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.30802/AALAS-JAALAS-19-000013",
language = "English (US)",
volume = "58",
pages = "597--600",
journal = "Journal of the American Association for Laboratory Animal Science",
issn = "1559-6109",
publisher = "American Association for Laboratory Animal Science",
number = "5",

}

TY - JOUR

T1 - Lack of absorption of a sustained-release buprenorphine formulation administered subcutaneously to athymic nude rats

AU - Douglas Page, C.

AU - Sarabia-Estrada, Rachel

AU - Jay Hoffman, R.

AU - Lo, Chih Ping

AU - Gades, Naomi M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.

AB - Female athymic nude rats (Rattus norvegicus; n = 45; age, 6 wk) were used in an IACUC-approved protocol to investigate mechanisms and potential treatments associated with brain, spine, and spinal cord metastases from triple negative breast cancer. The analgesic plan included the use of buprenorphine SR LAB (0.6 mg/kg; 0.11 mL/rat) subcutaneously and an oral NSAID delivered via the water. Thirty-seven rats reached the experimental end point at 3 mo after xenotransplantation and were euthanized for tissue harvest. Grossly, all 37 rats had nodules in the subcutis over the shoulders; these were identified as small, cystic structures (diameter, approximately 0.25 cm). The cysts and haired skin were submitted for LC-MS/MS (liquid chromatography-tandem mass spectrometry) and histopathology. Histologically, the cysts were lined by fibrous connective tissue mildly infiltrated by macrophages, lymphocytes, and plasma cells. Adjacent blood vessels were rimmed by a mild infiltrate of lymphocytes and plasma cells. The cysts contained variable accumulations of a light pink, proteinaceous fluid. The cause for the cysts could not be determined histologically; there was no evidence of neoplasia. LC-MS/MS analysis revealed that the cysts contained buprenorphine. We hypothesize that the lack of T cells and a cell-mediated immune response in these rats prevented the dissolution of the vehicle and absorption of the buprenorphine. The manufacturer provides a cautionary statement regarding the use of this formulation in nude mice due to skin reactions, but to our knowledge, this report is the first description of an apparent lack of absorption of the drug in immunodeficient animals.

UR - http://www.scopus.com/inward/record.url?scp=85074591862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074591862&partnerID=8YFLogxK

U2 - 10.30802/AALAS-JAALAS-19-000013

DO - 10.30802/AALAS-JAALAS-19-000013

M3 - Article

AN - SCOPUS:85074591862

VL - 58

SP - 597

EP - 600

JO - Journal of the American Association for Laboratory Animal Science

JF - Journal of the American Association for Laboratory Animal Science

SN - 1559-6109

IS - 5

ER -