Pharmacokinetics of preoperative intraperitoneal 5-FU in patients with pancreatic ductal adenocarcinoma

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Öman, MikaelUmeå universitet,Kirurgi (author)

Pharmacokinetics of preoperative intraperitoneal 5-FU in patients with pancreatic ductal adenocarcinoma

Article/chapterEnglish2021

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2021-06-16
Springer Science and Business Media LLC,2021

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LIBRIS-ID:oai:gup.ub.gu.se/306704
https://gup.ub.gu.se/publication/306704URI
https://doi.org/10.1007/s00280-021-04318-xDOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-185075URI

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Language:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kirurgi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Surgery hsv//eng
5-Fluorouracil
Intraperitoneal chemotherapy
Pancreatic cancer
Pharmacokinetics
Gene expression
organic anion transporter-2
phase-i
5-fluorouracil
multicenter
gemcitabine
inhibition
resistance
chemotherapy
vasopressin
modulation
Oncology
Pharmacology & Pharmacy
5-Fluorouracil

Added entries (persons, corporate bodies, meetings, titles ...)

Wettergren, Yvonne,1957Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xwetyv (author)
Odin, Elisabeth,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xodiel (author)
Westermark, SofiaUmeå universitet,Kirurgi,Department of Surgery, Örnsköldsviks sjukhus, Örnsköldsvik, Sweden(Swepub:umu)soawek02 (author)
Naredi, Peter,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xnarpe (author)
Hemmingsson, Oskar,1975-Umeå universitet,Kirurgi(Swepub:umu)osrhen96 (author)
Taflin, HelenaGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery(Swepub:gu)xtafhe (author)
Umeå universitetKirurgi (creator_code:org_t)

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