Lipiodol does not affect the tissue distribution of intravenous doxorubicin infusion in pigs

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 (Kp) 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 Kp. Lipiodol had no effect on the Kp 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.