title: Idarubicin-loaded ONCOZENE drug-eluting embolic agents for chemoembolization of hepatocellular carcinoma: in vitro loading and release and in vivo pharmacokinetics.
abstract: OBJECTIVE
  To present in vitro loading and release characteristics of idarubicin with ONCOZENE (CeloNova BioSciences, Inc, San Antonio, Texas) drug-eluting embolic (DEE) agents and in vivo pharmacokinetics data after transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents in patients with hepatocellular carcinoma.
  
  
  METHODS
  Loading efficacy of idarubicin with ONCOZENE DEE agents 100 µm and DC Bead (Biocompatibles UK Ltd, Farnham, United Kingdom) DEE agents 100-300 µm was monitored at 10, 20, and 30 minutes loading time by high-pressure liquid chromatography. A T-apparatus was used to monitor the release of idarubicin from the two types of DEE agents over 12 hours. Clinical and 24-hour pharmacokinetics data were recorded after transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents in four patients with unresectable hepatocellular carcinoma.
  
  
  RESULTS
  Idarubicin loading in ONCOZENE DEE agents was > 99% at 10 minutes. Time to reach 75% of the release plateau level was 37 minutes ± 6 for DC Bead DEE agents and 170 minutes ± 19 for ONCOZENE DEE agents both loaded with idarubicin 10 mg/mL. After transarterial chemoembolization with idarubicin-loaded ONCOZENE DEE agents, three partial responses and one complete response were observed with only two asymptomatic grade 3 biologic adverse events. Median time to maximum concentration for idarubicin in patients was 10 minutes, and mean maximum concentration was 4.9 µg/L ± 1.7. Mean area under the concentration-time curve from 0-24 hours was equal to 29.5 µg.h/L ± 20.5.
  
  
  CONCLUSIONS
  ONCOZENE DEE agents show promising results with very fast loading ability, a favorable in vivo pharmacokinetics profile with a sustained release of idarubicin during the first 24 hours, and encouraging safety and responses. Histopathologic and clinical studies are needed to evaluate idarubicin release around the DEE agents in tumor tissue and to confirm safety and efficacy.
authors.affiliation: Department of Radiology, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, Montpellier 34295, France. Electronic address: b-guiu@chu-montpellier.fr.
authors.forename: Boris
authors.initials: B
authors.lastname: Guiu
authors.affiliation: Department of Pharmacy, Georges-François Leclerc Anticancer Center, Dijon, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: CeloNova BioSciences, Inc, San Antonio, Texas.
authors.forename: Sven
authors.initials: S
authors.lastname: Reinhardt
authors.affiliation: Department of Radiology, University Hospital, Caen, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Fohlen
authors.affiliation: CeloNova BioSciences, Inc, San Antonio, Texas.
authors.forename: Theresa
authors.initials: T
authors.lastname: Pohl
authors.affiliation: Department of Pharmacology-Toxicology, University Hospital, Dijon, France.
authors.forename: Maëva
authors.initials: M
authors.lastname: Wendremaire
authors.affiliation: Department of Radiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Alban
authors.initials: A
authors.lastname: Denys
authors.affiliation: CeloNova BioSciences, Inc, San Antonio, Texas.
authors.forename: Jacques
authors.initials: J
authors.lastname: Blümmel
authors.affiliation: Department of Pharmacy, University Hospital, Dijon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boulin
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000628:therapy; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004058:Diffusion; D006490:Hemostatics / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000097:blood* / Q000628:therapy; D008297:Male; D008657:Metabolic Clearance Rate; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D006490:Hemostatics; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D015255:Idarubicin