title: In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation.
abstract: OBJECTIVE
  The chemotherapy agent gemcitabine is currently administered intravenously because the drug has poor oral bioavailability. In order to assess the pharmacokinetics and antitumor activity of D07001-F4, a new self-microemulsifying oral drug delivery system preparation of gemcitabine, this study was performed to compare the effect of D07001-F4 with administered gemcitabine in vitro and in vivo.
  
  
  METHODS
  D07001-F4 pharmacokinetics was examined by evaluation of in vitro deamination of D07001-F4 and gemcitabine hydrochloride by recombinant human cytidine deaminase (rhCDA) and in vivo evaluation of D07001-F4 pharmacokinetics in mice. Antitumor activity was evaluated by comparing the effect of D07001-F4 and gemcitabine hydrochloride in inhibiting growth in nine cancer cell lines and by examining the effect of D07001-F4 and gemcitabine in two xenograft tumor models in mice.
  
  
  RESULTS
  In vitro deamination of D07001-F4 by rhCDA was 3.3-fold slower than deamination of gemcitabine hydrochloride. Growth inhibition by D07001-F4 of 7 of the 8 cancer cell lines was increased compared with that seen with gemcitabine hydrochloride, and D07001-F4 inhibited the growth of pancreatic and colon cancer xenografts. In vivo pharmacokinetics showed the oral bioavailability of D07001-F4 to be 34%.
  
  
  CONCLUSIONS
  D07001-F4 was effective against several cancer types, was metabolized more slowly than gemcitabine hydrochloride, and exhibited enhanced oral bioavailability.
authors.affiliation: InnoPharmax Inc, 9F, No 22, Lane 478, Rueiguang Rd, Neihu District, Taipei 11492, Taiwan.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Hao
authors.forename: Jong-Jing
authors.initials: JJ
authors.lastname: Wang
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Hsueh
authors.forename: Pei-Jing
authors.initials: PJ
authors.lastname: Hsu
authors.forename: Li-Chien
authors.initials: LC
authors.lastname: Chang
authors.forename: Chang-Shan
authors.initials: CS
authors.lastname: Hsu
authors.forename: Kuang-Yang
authors.initials: KY
authors.lastname: Hsu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine