IDN5109, a taxane with oral bioavailability and potent antitumor activity

Maria Ines Nicoletti, Tina Colombo, Cosmo Rossi, Caterina Monardo, Stefania Stura, Massimo Zucchetti, Antonella Riva, Paolo Morazzoni, Maria Benedetta Donati, Ezio Bombardelli, Maurizio D'Incalci, Raffaella Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

IDN5109 is a new taxane, derived from 14β-hydroxy-10-deacetylbaccatin III, selected for its lack of cross-resistance in tumor cell lines expressing the multidrug resistant phenotype. Because, unlike paclitaxel, IDN5109 is a poor substrate for P-glycoprotein, we hypothesized that IDN5109 given p.o. could improve bioavailability compared with paclitaxel. Here, we studied the p.o. and i.v. pharmacokinetics of IDN5109 together with its antitumor activity. Using a high-performance liquid chromatography method, the bioavailability of IDN5109 was determined to be 48% after oral delivery. IDN5109 given p.o. was highly active against the two human ovarian carcinoma xenografts 1A9 and HOC18 (90-100% tumor regressions) and showed significant activity on the paclitaxel-resistant MNB-PTX1 xenograft (10% tumor regressions). The p.o. administration was as active as the i.v. route at doses reflecting the pharmacokinetic data. IDN5109 is the first taxane with good oral bioavailability and potent antitumor activity and represents a potential candidate for clinical investigation.

Original languageEnglish
Pages (from-to)842-846
Number of pages5
JournalCancer Research
Volume60
Issue number4
Publication statusPublished - Feb 15 2000

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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