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.
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.
Authors: Colin Yee; David McCoy; Jay Yu; Aaron Losey; Caroline Jordan; Terilyn Moore; Carol Stillson; Hee Jeung Oh; Bridget Kilbride; Shuvo Roy; Anand Patel; Mark W Wilson; Steven W Hetts Journal: Radiol Imaging Cancer Date: 2019-09-27