Objectives: In liver cancer treatment, lipiodol is used as a pharmaceutical excipient to improve delivery of the cytostatic drug doxorubicin (DOX). As DOX and its metabolite doxorubicinol (DOXol) cause serious off-target adverse effects, we investigated the effects of drug-free lipiodol or ciclosporin (CsA) on the tissue distribution (K ) of DOX and DOXol in relevant pig tissues.
Methods: Four treatment groups (TI-TIV) all received an intravenous DOX solution at 0 and 200 min. Before the second dose, the pigs received a portal vein infusion of saline (TI), lipiodol (TII), CsA (TIII) or lipiodol and CsA (TIV). After 6 h, the pigs were euthanised, and liver, kidney, heart and intestine samples were collected and analysed.
Key Findings: The tissue DOX concentrations were highest in the kidney (TI-TIV). All the investigated tissues showed extensive DOX K . Lipiodol had no effect on the K of DOX to any of the tissues. However, the tissue concentrations of DOX were increased by CsA (in liver, kidney and intestine, P < 0.05).
Conclusion: Lipiodol injected into the portal vein does not affect the tissue distribution of DOX and DOXol.
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http://dx.doi.org/10.1111/jphp.12665 | DOI Listing |
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