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Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models
Vocacapsaicin is a novel prodrug of trans‐capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) being developed as a nonopioid, long‐lasting, site‐specific treatment for postsurgical pain management. The objective of these studies was to examine the safety and tolerability of vocacapsaicin in an osteot...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790453/ https://www.ncbi.nlm.nih.gov/pubmed/35128722 http://dx.doi.org/10.1002/jor.25271 |
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author | Knotts, Tarra Mease, Kirsten Sangameswaran, Lakshmi Felx, Melanie Kramer, Susan Donovan, John |
author_facet | Knotts, Tarra Mease, Kirsten Sangameswaran, Lakshmi Felx, Melanie Kramer, Susan Donovan, John |
author_sort | Knotts, Tarra |
collection | PubMed |
description | Vocacapsaicin is a novel prodrug of trans‐capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) being developed as a nonopioid, long‐lasting, site‐specific treatment for postsurgical pain management. The objective of these studies was to examine the safety and tolerability of vocacapsaicin in an osteotomy model in two animal species and to evaluate bone healing parameters. Rats undergoing unilateral femoral osteotomy received a single perioperative administration (by instillation) of vocacapsaicin (vehicle, 0.15, 0.3, and 0.6 mg/kg). Rabbits undergoing unilateral ulnar osteotomy received a single perioperative administration (by infiltration and instillation) of vocacapsaicin (vehicle, 0.256 and 0.52 mg) alone or in combination with 0.5% ropivacaine. Clinical signs, body weights, food consumption, radiography, histopathologic examinations, ex vivo bone mineral density measurements (rats only), and biomechanical testing were evaluated at 4 and 8 weeks in rats and at 2 and 10 weeks in rabbits. Plasma samples were also collected in rabbits. There were no vocacapsaicin‐related effects on mortality, clinical observations, body weight, or food consumption in either species. Systemic exposure to vocacapsaicin and its metabolites, including capsaicin, was transient. In rats, vocacapsaicin was devoid of deleterious effects on bone healing parameters, and there was a trend for enhanced bone healing in rats treated with the mid‐dose. In rabbits, vocacapsaicin administered alone or in combination with ropivacaine did not adversely affect bone healing parameters. In conclusion, a single perioperative administration of vocacapsaicin in unilateral osteotomy models was well tolerated, locally and systemically, supporting its continued development as a novel, nonopioid treatment for postsurgical pain management. |
format | Online Article Text |
id | pubmed-9790453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97904532022-12-28 Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models Knotts, Tarra Mease, Kirsten Sangameswaran, Lakshmi Felx, Melanie Kramer, Susan Donovan, John J Orthop Res Research Articles Vocacapsaicin is a novel prodrug of trans‐capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) being developed as a nonopioid, long‐lasting, site‐specific treatment for postsurgical pain management. The objective of these studies was to examine the safety and tolerability of vocacapsaicin in an osteotomy model in two animal species and to evaluate bone healing parameters. Rats undergoing unilateral femoral osteotomy received a single perioperative administration (by instillation) of vocacapsaicin (vehicle, 0.15, 0.3, and 0.6 mg/kg). Rabbits undergoing unilateral ulnar osteotomy received a single perioperative administration (by infiltration and instillation) of vocacapsaicin (vehicle, 0.256 and 0.52 mg) alone or in combination with 0.5% ropivacaine. Clinical signs, body weights, food consumption, radiography, histopathologic examinations, ex vivo bone mineral density measurements (rats only), and biomechanical testing were evaluated at 4 and 8 weeks in rats and at 2 and 10 weeks in rabbits. Plasma samples were also collected in rabbits. There were no vocacapsaicin‐related effects on mortality, clinical observations, body weight, or food consumption in either species. Systemic exposure to vocacapsaicin and its metabolites, including capsaicin, was transient. In rats, vocacapsaicin was devoid of deleterious effects on bone healing parameters, and there was a trend for enhanced bone healing in rats treated with the mid‐dose. In rabbits, vocacapsaicin administered alone or in combination with ropivacaine did not adversely affect bone healing parameters. In conclusion, a single perioperative administration of vocacapsaicin in unilateral osteotomy models was well tolerated, locally and systemically, supporting its continued development as a novel, nonopioid treatment for postsurgical pain management. John Wiley and Sons Inc. 2022-02-06 2022-10 /pmc/articles/PMC9790453/ /pubmed/35128722 http://dx.doi.org/10.1002/jor.25271 Text en © 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Knotts, Tarra Mease, Kirsten Sangameswaran, Lakshmi Felx, Melanie Kramer, Susan Donovan, John Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title | Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title_full | Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title_fullStr | Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title_full_unstemmed | Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title_short | Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
title_sort | pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790453/ https://www.ncbi.nlm.nih.gov/pubmed/35128722 http://dx.doi.org/10.1002/jor.25271 |
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