Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model

Elisabeth K. Petersen; Mats Bue; Christina Harlev; Andrea R. Jørgensen; Anne Schmedes; Pelle Hanberg; Lone K. Petersen; Maiken Stilling

doi:10.1515/pp-2022-0110

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model

Elisabeth K. Petersen^*, Mats Bue, Christina Harlev, Andrea R. Jørgensen, Anne Schmedes, Pelle Hanberg, Lone K. Petersen, Maiken Stilling

^*Corresponding author for this work

Department of Clinical Medicine - Orthopaedic surgery

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

3 Citations (Scopus)

Abstract

Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·μg/mL), mean Cmax (range: 10.6-26.0 μg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 μg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

Original language	English
Journal	Pleura and Peritoneum
Volume	7
Issue	3
Pages (from-to)	117-125
Number of pages	9
ISSN	2364-7671
DOIs	https://doi.org/10.1515/pp-2022-0110
Publication status	Published - Sept 2022

Keywords

carboplatin
hyperthermic intraperitoneal chemotherapy
microdialysis
pharmacokinetics

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10.1515/pp-2022-0110Licence: CC BY

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@article{5ebe11cc51ba4f509e7b9ccb4bae1821,

title = "Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model",

abstract = "Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·μg/mL), mean Cmax (range: 10.6-26.0 μg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 μg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.",

keywords = "carboplatin, hyperthermic intraperitoneal chemotherapy, microdialysis, pharmacokinetics",

author = "Petersen, {Elisabeth K.} and Mats Bue and Christina Harlev and J{\o}rgensen, {Andrea R.} and Anne Schmedes and Pelle Hanberg and Petersen, {Lone K.} and Maiken Stilling",

note = "Publisher Copyright: {\textcopyright} 2022 Elisabeth K. Petersen et al., published by De Gruyter, Berlin/Boston.",

year = "2022",

month = sep,

doi = "10.1515/pp-2022-0110",

language = "English",

volume = "7",

pages = "117--125",

journal = "Pleura and Peritoneum",

issn = "2364-7671",

publisher = "Walter de Gruyter GmbH",

number = "3",

}

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model. / Petersen, Elisabeth K.; Bue, Mats ; Harlev, Christina et al.
In: Pleura and Peritoneum, Vol. 7, No. 3, 09.2022, p. 117-125.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model

AU - Petersen, Elisabeth K.

AU - Bue, Mats

AU - Harlev, Christina

AU - Jørgensen, Andrea R.

AU - Schmedes, Anne

AU - Hanberg, Pelle

AU - Petersen, Lone K.

AU - Stilling, Maiken

PY - 2022/9

Y1 - 2022/9

N2 - Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·μg/mL), mean Cmax (range: 10.6-26.0 μg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 μg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

AB - Objectives: Peritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model. Methods: Eight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h. Results: No statistically significant differences in mean AUC0-last (range: 2,657-5,176 min·μg/mL), mean Cmax (range: 10.6-26.0 μg/mL) and mean Tmax (range: 105-206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9-9.9 μg/mL across the investigated solid tissues. Conclusions: Equal carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

KW - carboplatin

KW - hyperthermic intraperitoneal chemotherapy

KW - microdialysis

KW - pharmacokinetics

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DO - 10.1515/pp-2022-0110

M3 - Journal article

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AN - SCOPUS:85138631955

SN - 2364-7671

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SP - 117

EP - 125

JO - Pleura and Peritoneum

JF - Pleura and Peritoneum

IS - 3

ER -

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure - Assessment in a novel porcine model

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