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In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model
BACKGROUND: The pharmacokinetic properties and clinical advantages of the local anesthetic chloroprocaine are well known. Here, we studied the pharmacokinetic profile of a new hydrogel device loaded with chloroprocaine to investigate the potential advantages of this new strategy for postoperative pa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231440/ https://www.ncbi.nlm.nih.gov/pubmed/30510443 http://dx.doi.org/10.2147/JPR.S180163 |
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author | De Gregori, Simona De Gregori, Manuela Bloise, Nora Bugada, Dario Molinaro, Mariadelfina Filisetti, Claudia Allegri, Massimo Schatman, Michael E Cobianchi, Lorenzo |
author_facet | De Gregori, Simona De Gregori, Manuela Bloise, Nora Bugada, Dario Molinaro, Mariadelfina Filisetti, Claudia Allegri, Massimo Schatman, Michael E Cobianchi, Lorenzo |
author_sort | De Gregori, Simona |
collection | PubMed |
description | BACKGROUND: The pharmacokinetic properties and clinical advantages of the local anesthetic chloroprocaine are well known. Here, we studied the pharmacokinetic profile of a new hydrogel device loaded with chloroprocaine to investigate the potential advantages of this new strategy for postoperative pain (POP) relief. MATERIALS AND METHODS: We performed both in vitro and in vivo analyses by considering plasma samples of four piglets receiving slow-release chloroprocaine. To quantify chloroprocaine and its inactive metabolite 4-amino-2-chlorobenzoic acid (ACBA), a HPLC–tandem mass spectrometry (HPLC-MS/MS) analytical method was used. Serial blood samples were collected over 108 hours, according to the exposure time to the device. RESULTS: Chloroprocaine was consistently found to be below the lower limit of quantification, even though a well-defined peak was observed in every chromatogram at an unexpected retention time. Concerning ACBA, we found detectable plasma concentrations between T(0) and T(12h), with a maximum plasma concentration (C(max)) observed 3 hours after the device application. In the in vitro analyses, the nanogel remained in contact with plasma at 37°C for 90 minutes, 3 hours, 1 day, and 7 days. Chloroprocaine C(max) was identified 1 day following exposure and C(min) after 7 days, respectively. Additionally, ACBA reached the C(max) following 7 days of exposure. CONCLUSION: A thorough review of the literature indicates that this is the first study analyzing both in vivo and in vitro pharmacokinetic profiles of a chloroprocaine hydrogel device and is considered as a pilot study on the feasibility of including this approach to the management of POP. |
format | Online Article Text |
id | pubmed-6231440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62314402018-12-03 In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model De Gregori, Simona De Gregori, Manuela Bloise, Nora Bugada, Dario Molinaro, Mariadelfina Filisetti, Claudia Allegri, Massimo Schatman, Michael E Cobianchi, Lorenzo J Pain Res Original Research BACKGROUND: The pharmacokinetic properties and clinical advantages of the local anesthetic chloroprocaine are well known. Here, we studied the pharmacokinetic profile of a new hydrogel device loaded with chloroprocaine to investigate the potential advantages of this new strategy for postoperative pain (POP) relief. MATERIALS AND METHODS: We performed both in vitro and in vivo analyses by considering plasma samples of four piglets receiving slow-release chloroprocaine. To quantify chloroprocaine and its inactive metabolite 4-amino-2-chlorobenzoic acid (ACBA), a HPLC–tandem mass spectrometry (HPLC-MS/MS) analytical method was used. Serial blood samples were collected over 108 hours, according to the exposure time to the device. RESULTS: Chloroprocaine was consistently found to be below the lower limit of quantification, even though a well-defined peak was observed in every chromatogram at an unexpected retention time. Concerning ACBA, we found detectable plasma concentrations between T(0) and T(12h), with a maximum plasma concentration (C(max)) observed 3 hours after the device application. In the in vitro analyses, the nanogel remained in contact with plasma at 37°C for 90 minutes, 3 hours, 1 day, and 7 days. Chloroprocaine C(max) was identified 1 day following exposure and C(min) after 7 days, respectively. Additionally, ACBA reached the C(max) following 7 days of exposure. CONCLUSION: A thorough review of the literature indicates that this is the first study analyzing both in vivo and in vitro pharmacokinetic profiles of a chloroprocaine hydrogel device and is considered as a pilot study on the feasibility of including this approach to the management of POP. Dove Medical Press 2018-11-08 /pmc/articles/PMC6231440/ /pubmed/30510443 http://dx.doi.org/10.2147/JPR.S180163 Text en © 2018 De Gregori et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research De Gregori, Simona De Gregori, Manuela Bloise, Nora Bugada, Dario Molinaro, Mariadelfina Filisetti, Claudia Allegri, Massimo Schatman, Michael E Cobianchi, Lorenzo In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title | In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title_full | In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title_fullStr | In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title_full_unstemmed | In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title_short | In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
title_sort | in vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231440/ https://www.ncbi.nlm.nih.gov/pubmed/30510443 http://dx.doi.org/10.2147/JPR.S180163 |
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