Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model
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Interventional Radiology - Original Article
P: 235-240
May 2015

Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model

Diagn Interv Radiol 2015;21(3):235-240
1. Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois, USA
2. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, Chicago, Illinois, USA
3. Department of Radiology, University of Illinois Hospital and Health Sciences System, Chicago, Illinois, USA
No information available.
No information available
Received Date: 02.09.2014
Accepted Date: 04.11.2014
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ABSTRACT

PURPOSE

Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model.

METHODS

A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification.

RESULTS

Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10–18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution.

CONCLUSION

While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.