title: Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE.
  
  
  CONCLUSIONS
  • 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.
authors.affiliation: EA 4184, University of Burgundy and Department of Pharmacy, Dijon University Hospital, 14 rue Gaffarel, 21000, Dijon, France. mathieuboulin@yahoo.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boulin
authors.affiliation: EA 4184, University of Burgundy and Department of Pharmacy, Georges-François Leclerc Anticancer Center, Dijon, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Radiology, Saint-Eloi University Hospital, Montpellier, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Delhom
authors.affiliation: Department of Radiology, University Hospital, Dijon, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cercueil
authors.affiliation: Department of Pharmacoloy-Toxicology, University Hospital, Dijon, France.
authors.forename: Maëva
authors.initials: M
authors.lastname: Wendremaire
authors.affiliation: EA4553 Institut Claudius-Regaud, University of Toulouse, Toulouse, France.
authors.forename: Diane-Charlotte
authors.initials: DC
authors.lastname: Imbs
authors.affiliation: Department of Radiology, University Hospital, Caen, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Fohlen
authors.affiliation: Department of General and Liver Transplant Surgery, Saint-Eloi University Hospital, Montpellier, France.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Panaro
authors.affiliation: Department of General and Liver Transplant Surgery, Saint-Eloi University Hospital, Montpellier, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Herrero
authors.affiliation: Department of Radiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Alban
authors.initials: A
authors.lastname: Denys
authors.affiliation: Department of Radiology, Saint-Eloi University Hospital, Montpellier, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Guiu
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004998:Ethiodized Oil / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004998:Ethiodized Oil; D015255:Idarubicin
keywords: Hepatocellular carcinoma; Idarubicin; Lipiodol; Pharmacokinetics; Transarterial chemoembolisation