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Pharmacokinetics of...
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Öman, MikaelUmeå universitet,Kirurgi
(author)
Pharmacokinetics of preoperative intraperitoneal 5-FU in patients with pancreatic ductal adenocarcinoma
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-06-16
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Springer Science and Business Media LLC,2021
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LIBRIS-ID:oai:gup.ub.gu.se/306704
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https://gup.ub.gu.se/publication/306704URI
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https://doi.org/10.1007/s00280-021-04318-xDOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-185075URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Purpose The aim was to investigate the pharmacokinetics of preoperatively administered intraperitoneal (IP) 5-FU in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by analyzing levels of 5-FU and target metabolites in peritoneal fluid, plasma, liver, lymph nodes, pancreatic tumour, and pancreatic tissue. These results were correlated to expression of genes encoding enzymes of the 5-FU pathway and cell membrane transporters of 5-FU and FdUMP. Methods Twenty-two patients with PDAC were treated with IP 5-FU before surgery. The postoperative treatment followed a routine clinical protocol. 5-FU and its metabolites were analyzed by LC-MS/MS. The expression of genes encoding enzymes and transporters in the 5-FU pathway was analyzed by qPCR. Results After IP treatment, 5-FU could be detected in plasma, lymph nodes, liver, pancreatic tumour, and pancreatic tissue. The highest 5-FU concentration was found in the liver, also expressing high levels of the 5-FU transporter OAT2. 5-FU was converted to active FdUMP in all tissues and the highest concentration was measured in lymph nodes, liver and pancreatic tumour (18.5, 6.1 and 6.7 pmol/g, respectively). There was a correlation between the FdUMP and dUr levels in lymph nodes (r = 0.70, p = 0.0076). In tumours, there was an association between OAT2 expression and FdUMP concentration. Conclusion The study shows uptake of IP 5-FU and drug metabolism to active FdUMP in pancreatic tumour, liver, and lymph nodes. Extended studies are warranted to evaluate the IP route for 5-FU administration in PDAC patients.
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Wettergren, Yvonne,1957Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xwetyv
(author)
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Odin, Elisabeth,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xodiel
(author)
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Westermark, SofiaUmeå universitet,Kirurgi,Department of Surgery, Örnsköldsviks sjukhus, Örnsköldsvik, Sweden(Swepub:umu)soawek02
(author)
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Naredi, Peter,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xnarpe
(author)
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Hemmingsson, Oskar,1975-Umeå universitet,Kirurgi(Swepub:umu)osrhen96
(author)
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Taflin, HelenaGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xtafhe
(author)
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Umeå universitetKirurgi
(creator_code:org_t)
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In:Cancer Chemotherapy and Pharmacology: Springer Science and Business Media LLC88, s. 619-6310344-57041432-0843
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