Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study.

Cancer Chemotherapy and Pharmacology
Inge R H M KoningsWalter J Loos

Abstract

Response to anticancer therapy is believed to be directly related to the concentration of the anticancer drug in the tumor itself. Assessment of intra-tumor drug pharmacokinetics can be helpful to gain more insight into mechanisms involved in the (in)sensitivity of tumors to anticancer therapy. We explored the pharmacokinetics of 5-fluorouracil in both plasma and tumor tissue during a 5-day continuous infusion of 5-fluorouracil in patients with cancer. Sampling for measurement of 5-fluorouracil in tumor tissue was performed using microdialysis. In seven patients with an accessible (sub)cutaneous tumor treated with a continuous 5-fluorouracil infusion, plasma and microdialysate samples from tumor and normal adipose tissue were collected over a period of 5 days. For six patients, drug concentrations in both tumor tissue and plasma were available. Concentration-time curves of unbound 5-fluorouracil were lower in tumor tissue compared to the curves in plasma, but exposure ratios of tumor tissue versus plasma increased during the 5-day infusion period. The presence of circadian rhythmicity of 5-fluorouracil pharmacokinetics in the tumor itself was demonstrated as 5-fluorouracil concentrations in tumor extracellular fluid were higher...Continue Reading

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Citations

Jan 24, 2014·Clinical Pharmacokinetics·Francine Johansson AzeredoHartmut Derendorf
Nov 14, 2013·International Journal of Pharmaceutics·Taís Gratieri, Yogeshvar N Kalia
Oct 28, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Shinji KobuchiToshiyuki Sakaeda
Dec 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jana PortnowKaren S Aboody
Sep 4, 2020·British Journal of Clinical Pharmacology·Rémi LonguespéeWalter E Haefeli
Dec 24, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Florian SlimanoSylvain Dukic

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