title: In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma.
abstract: Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol and their short-term safety and antitumor effects were also evaluated. In this open, prospective, nonrandomized multicenter study, LIPDOX (n = 13) or DEBDOX (n = 12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmaxand AUC0-24 hfor DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p < 0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.
authors.affiliation: Department of Pharmacy, Uppsala University , Box 580, 751 23 Uppsala, Sweden.
authors.forename: Elsa
authors.identifier: 0000-0003-0271-4536
authors.initials: E
authors.lastname: Lilienberg
authors.affiliation: Department of Pharmacy, Uppsala University , Box 580, 751 23 Uppsala, Sweden.
authors.forename: Ilse R
authors.initials: IR
authors.lastname: Dubbelboer
authors.affiliation: Department of Radiology, Karolinska University Hospital in Huddinge , Stockholm, Sweden.|Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet , Stockholm, Sweden.
authors.forename: Amar
authors.initials: A
authors.lastname: Karalli
authors.affiliation: Department of Radiology, Karolinska University Hospital in Huddinge , Stockholm, Sweden.|Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet , Stockholm, Sweden.
authors.forename: Rimma
authors.initials: R
authors.lastname: Axelsson
authors.affiliation: Department of Radiology, Karolinska University Hospital in Huddinge , Stockholm, Sweden.|Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet , Stockholm, Sweden.
authors.forename: Torkel B
authors.initials: TB
authors.lastname: Brismar
authors.affiliation: Department of Radiology, Uppsala University Hospital, Uppsala University , 751 85 Uppsala, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ebeling Barbier
authors.affiliation: Department of Surgical Sciences, Uppsala University Hospital, Uppsala University , 751 85 Uppsala, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Norén
authors.affiliation: Department of Surgical Sciences, Uppsala University Hospital, Uppsala University , 751 85 Uppsala, Sweden.
authors.forename: Frans
authors.initials: F
authors.lastname: Duraj
authors.affiliation: Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA) , 751 89 Uppsala, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hedeland
authors.affiliation: Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA) , 751 89 Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Bondesson
authors.affiliation: Department of Pharmacy, Uppsala University , Box 580, 751 23 Uppsala, Sweden.
authors.forename: Erik
authors.identifier: 0000-0003-4318-6039
authors.initials: E
authors.lastname: Sjögren
authors.affiliation: Unit of Gastroenterology, Deptartment of Internal Medicine Huddinge, Karolinska Institutet , Stockholm, Sweden.|Department of Digestive Diseases, Karolinska University Hospital in Huddinge , Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Stål
authors.affiliation: Department of Radiology, Uppsala University Hospital, Uppsala University , 751 85 Uppsala, Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Nyman
authors.affiliation: Department of Pharmacy, Uppsala University , Box 580, 751 23 Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000627:therapeutic use*; D004998:Ethiodized Oil / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000903:Antibiotics, Antineoplastic; D004655:Emulsions; D004998:Ethiodized Oil
keywords: doxorubicin; doxorubicinol; drug eluting beads; hepatocellular carcinoma; lipiodol; liver cancer; local delivery; local therapy; transarterial chemoembolization; transarterial infusion chemotherapy