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

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.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Gao J,Zhen R,Liao H,Zhuang W,Guo W

doi

10.3892/ol.2018.8242

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

7175-7181

issue

5

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-8242

journal_volume

15

pub_type

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