IDN5109, a taxane with oral bioavailability and potent antitumor activity

IDN5109 is a new taxane, derived from 14 beta-hydroxy-10-deacetylbaccatin I II, selected for its lack of cross-resistance in tumor cell lines expressin g 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 bioava ilability of IDN5109 was determined to be 48% after oral delivery. IDN5109 given p.o. was highly active against the two human ovarian carcinoma xenogr afts 1A9 and HOC18 (90-100% tumor regressions) and showed significant activ ity on the paclitaxel-resistant MNB-PTX1 xenograft (10% tumor regressions). The p.o. administration was as active as the i.v. route at doses reflectin g the pharmaco-kinetic data, IDN5109 is the first taxane with good oral bio availability and potent antitumor activity and represents a potential candi date for clinical investigation.