Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin
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Serval ID
serval:BIB_EEF758835DF3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin
Journal
Eur Radiol
ISSN-L
1432-1084 (Electronic) 0938-7994 (Linking)
Publication state
Published
Issued date
2015
Notes
Boulin, Mathieu
Schmitt, Antonin
Delhom, Elisabeth
Cercueil, Jean-Pierre
Wendremaire, Maeva
Imbs, Diane-Charlotte
Fohlen, Audrey
Panaro, Fabrizio
Herrero, Astrid
Denys, Alban
Guiu, Boris
ENG
2015/06/11 06:00
Eur Radiol. 2015 Jun 11.
Schmitt, Antonin
Delhom, Elisabeth
Cercueil, Jean-Pierre
Wendremaire, Maeva
Imbs, Diane-Charlotte
Fohlen, Audrey
Panaro, Fabrizio
Herrero, Astrid
Denys, Alban
Guiu, Boris
ENG
2015/06/11 06:00
Eur Radiol. 2015 Jun 11.
Abstract
OBJECTIVES: To investigate the relationship between the improved stability of an anticancer drug-lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC). METHODS: The stability of four doxorubicin- or idarubicin-lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval. RESULTS: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin-lipiodol (1:1 v:v), doxorubicin-lipiodol (1:2 v:v), idarubicin-lipiodol (1:1 v:v), and the idarubicin-lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin Cmax and AUC0-24h were 12.5 +/- 9.4 ng/mL and 52 +/- 16 ng/mL*h. Within 24 h after injection, 40 % of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months. CONCLUSION: This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE. KEY POINTS: * Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. * Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. * Preliminary safety and efficacy data for the idarubicin-lipiodol emulsion for TACE were encouraging.
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31/07/2015 8:23
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