In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model
Simona De Gregori,1 Manuela De Gregori,1–4 Nora Bloise,5,6 Dario Bugada,3,4,7 Mariadelfina Molinaro,1 Claudia Filisetti,8 Massimo Allegri,3,9 Michael E Schatman,3,10,11 Lorenzo Cobianchi12,13 1Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2018-11-01
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| Series: | Journal of Pain Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/in-vitro-and-in-vivo-quantification-of-chloroprocaine-release-from-an--peer-reviewed-article-JPR |
| _version_ | 1818133499530444800 |
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| author | De Gregori S De Gregori M Bloise N Bugada D Molinaro M Filisetti C Allegri M Schatman ME Cobianchi L |
| author_facet | De Gregori S De Gregori M Bloise N Bugada D Molinaro M Filisetti C Allegri M Schatman ME Cobianchi L |
| author_sort | De Gregori S |
| collection | DOAJ |
| description | Simona De Gregori,1 Manuela De Gregori,1–4 Nora Bloise,5,6 Dario Bugada,3,4,7 Mariadelfina Molinaro,1 Claudia Filisetti,8 Massimo Allegri,3,9 Michael E Schatman,3,10,11 Lorenzo Cobianchi12,13 1Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Study in Multidisciplinary Pain Research Group, Parma, Italy; 4Young Against Pain Group, Parma, Italy; 5Department of Molecular Medicine, Centre for Health Technologies, INSTM UdR of Pavia, University of Pavia, Pavia, Italy; 6Department of Occupational Medicine, Toxicology and Environmental Risks, Istituti Clinici Scientifici Maugeri, IRCCS, Lab of Nanotechnology, Pavia, Italy; 7Emergency and Intensive Care Department – ASST Papa Giovanni XXIII, Bergamo, Italy; 8“V. Buzzi” Children Hospital, Pediatric Surgery, Milan, Italy; 9Anesthesia and Intensive Care Service, IRCCS MultiMedica Hospital, Sesto San Giovanni, Milano, Italy; 10Research and Network Development, Boston Pain Care, Waltham, MA, USA; 11Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 12General Surgery Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 13Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 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 T0 and T12h, with a maximum plasma concentration (Cmax) 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 Cmax was identified 1 day following exposure and Cmin after 7 days, respectively. Additionally, ACBA reached the Cmax 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. Keywords: postoperative outcome, hydrogel device, chloroprocaine, ACBA, pharmacokinetics |
| first_indexed | 2024-12-11T08:53:42Z |
| format | Article |
| id | doaj.art-5dac526ec25f4a28a51b27c27754b11b |
| institution | Directory Open Access Journal |
| issn | 1178-7090 |
| language | English |
| last_indexed | 2024-12-11T08:53:42Z |
| publishDate | 2018-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Pain Research |
| spelling | doaj.art-5dac526ec25f4a28a51b27c27754b11b2022-12-22T01:13:56ZengDove Medical PressJournal of Pain Research1178-70902018-11-01Volume 112837284642116In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain modelDe Gregori SDe Gregori MBloise NBugada DMolinaro MFilisetti CAllegri MSchatman MECobianchi LSimona De Gregori,1 Manuela De Gregori,1–4 Nora Bloise,5,6 Dario Bugada,3,4,7 Mariadelfina Molinaro,1 Claudia Filisetti,8 Massimo Allegri,3,9 Michael E Schatman,3,10,11 Lorenzo Cobianchi12,13 1Clinical and Experimental Pharmacokinetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Study in Multidisciplinary Pain Research Group, Parma, Italy; 4Young Against Pain Group, Parma, Italy; 5Department of Molecular Medicine, Centre for Health Technologies, INSTM UdR of Pavia, University of Pavia, Pavia, Italy; 6Department of Occupational Medicine, Toxicology and Environmental Risks, Istituti Clinici Scientifici Maugeri, IRCCS, Lab of Nanotechnology, Pavia, Italy; 7Emergency and Intensive Care Department – ASST Papa Giovanni XXIII, Bergamo, Italy; 8“V. Buzzi” Children Hospital, Pediatric Surgery, Milan, Italy; 9Anesthesia and Intensive Care Service, IRCCS MultiMedica Hospital, Sesto San Giovanni, Milano, Italy; 10Research and Network Development, Boston Pain Care, Waltham, MA, USA; 11Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 12General Surgery Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 13Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy 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 T0 and T12h, with a maximum plasma concentration (Cmax) 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 Cmax was identified 1 day following exposure and Cmin after 7 days, respectively. Additionally, ACBA reached the Cmax 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. Keywords: postoperative outcome, hydrogel device, chloroprocaine, ACBA, pharmacokineticshttps://www.dovepress.com/in-vitro-and-in-vivo-quantification-of-chloroprocaine-release-from-an--peer-reviewed-article-JPRPostoperative painhydrogel devicechloroprocaineACBApharmacokinetics |
| spellingShingle | De Gregori S De Gregori M Bloise N Bugada D Molinaro M Filisetti C Allegri M Schatman ME Cobianchi L In vitro and in vivo quantification of chloroprocaine release from an implantable device in a piglet postoperative pain model Journal of Pain Research Postoperative pain hydrogel device chloroprocaine ACBA pharmacokinetics |
| 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 | Postoperative pain hydrogel device chloroprocaine ACBA pharmacokinetics |
| url | https://www.dovepress.com/in-vitro-and-in-vivo-quantification-of-chloroprocaine-release-from-an--peer-reviewed-article-JPR |
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