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Pharmacokinetics of...
Pharmacokinetics of preoperative intraperitoneal 5-FU in patients with pancreatic ductal adenocarcinoma
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- Öman, Mikael (author)
- Umeå universitet,Kirurgi
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- Wettergren, Yvonne, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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- Odin, Elisabeth, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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- Westermark, Sofia (author)
- Umeå universitet,Kirurgi,Department of Surgery, Örnsköldsviks sjukhus, Örnsköldsvik, Sweden
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- Naredi, Peter, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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- Hemmingsson, Oskar, 1975- (author)
- Umeå universitet,Kirurgi
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- Taflin, Helena (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Institute of Clinical Sciences, Department of Surgery
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(creator_code:org_t)
- 2021-06-16
- 2021
- English.
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 88, s. 619-631
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https://doi.org/10.1...
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Abstract
Subject headings
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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
- 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)
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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