Open Access

Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma

  • Authors:
    • Jian Gao
    • Rui Zhen
    • Hai Liao
    • Wenquan Zhuang
    • Wenbo Guo
  • View Affiliations

  • Published online on: March 12, 2018     https://doi.org/10.3892/ol.2018.8242
  • Pages: 7175-7181
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous studies concerning hepatic arterial infusion chemotherapy (HAIC) have been conducted by adopting regimens containing 5-fluorouracil (FU), with a favourable efficacy compared with conventional transcatheter arterial chemoembolisation (TACE) treatment; however, the detailed mechanism of HAIC remains unclear. The present study aimed to evaluate peripheral concentration time curves of 5‑FU administered through the hepatic artery, which may additionally explain the mechanism of action of HAIC. A total of 10 eligible patients underwent transcatheter arterial embolization and a 2‑day HAIC treatment regimen using a folinic acid, fluorouracil and oxaliplatin regimen. Peripheral venous blood sampling was performed in each patient prior to infusion, and at 0, 0.5, 1, 1.5, 2, 5, 10, 15, 22 and 23 h following the start of infusion. The blood sample at 0 h was analysed for dihydropyrimidine dehydrogenase (DPD) levels by high performance liquid chromatography, and the rest of the samples were analysed for 5‑FU by optimised liquid chromatography-mass spectrometry (LC‑MS). The lower limit of quantification of optimised LC‑MS for 5‑FU was 5 ng/ml. The steady-state plasma concentration of 5‑FU administered through the hepatic artery was achieved after 15 h. This concentration largely varied, ranging from 8.64‑152.00 ng/ml. Optimised LC‑MS may detect low concentrations of 5‑FU. The steady‑state concentration of 5‑FU administered through the hepatic artery was achieved after 15 h. DPD levels were analysed through determining the ratio of plasma uracil (U) and dihydrouracil (UH2) by HPLC, and the results indicated a mild DPD deficiency in the patients with HCC. These results may provide a basis for the explanation of the clinical efficacy of HAIC, and to additionally optimise its efficacy.
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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Gao J, Zhen R, Liao H, Zhuang W and Guo W: Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma. Oncol Lett 15: 7175-7181, 2018
APA
Gao, J., Zhen, R., Liao, H., Zhuang, W., & Guo, W. (2018). Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma. Oncology Letters, 15, 7175-7181. https://doi.org/10.3892/ol.2018.8242
MLA
Gao, J., Zhen, R., Liao, H., Zhuang, W., Guo, W."Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma". Oncology Letters 15.5 (2018): 7175-7181.
Chicago
Gao, J., Zhen, R., Liao, H., Zhuang, W., Guo, W."Pharmacokinetics of continuous transarterial infusion of 5-fluorouracil in patients with advanced hepatocellular carcinoma". Oncology Letters 15, no. 5 (2018): 7175-7181. https://doi.org/10.3892/ol.2018.8242