title: Novel iontophoretic administration method for local therapy of breast cancer.
abstract: Ductal drug therapy is a novel therapeutic approach for primary breast cancers, particularly those involving ductal carcinoma in situ lesions. Total or partial mastectomy with or without radiotherapy is the standard local therapy for primary breast cancer. Here, we propose a novel drug administration method for ductal drug therapy based on a drug delivery system (DDS) for primary breast cancer. This DDS was designed to deliver miproxifen phosphate (TAT-59), an antiestrogen drug, to ductal lesions via the milk duct, where carcinomas originate, more efficiently than systemic administration, using an iontophoretic technique applied to the nipple (IP administration). Autoradiography imaging confirmed that TAT-59 was directly delivered to the milk duct using IP administration. The plasma concentrations of TAT-59 and its active metabolite DP-TAT-59 were quite low with IP administration. The area under the curve value of DP-TAT-59 in the mammary tissue was approximately 3 times higher with IP administration than with oral administration, at a 6-fold lower dose, indicating higher availability of the drug delivered via DDS than via systemic administration. The low plasma concentrations would limit adverse effects to minor ones. These characteristics show that this DDS is suitable for the delivery of active DP-TAT-59 to ductal lesions.
authors.affiliation: Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan. m-komuro@taiho.co.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Komuro
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kanebako
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawahara
authors.forename: Takeshige
authors.initials: T
authors.lastname: Otoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitazato
authors.forename: Toshio
authors.initials: T
authors.lastname: Inagi
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy*; D004285:Dogs; D016503:Drug Delivery Systems; D004965:Estrogen Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008321:Mammary Glands, Animal / Q000378:metabolism; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen; C064635:TAT 59