Pharmacokinetic evaluation of three oral formulations of docetaxel boosted with ritonavir: two single-drug formulations vs. a fixed-dose combination tablet.

The ability to deliver the potent anti-cancer agent docetaxel via the oral route may enable the development of promising new treatment regimens with reduced toxicity, increased efficacy, and increased patient convenience. Recently, we were able to overcome the low oral bioavailability of docetaxel by concomitant administration of the pharmacokinetic booster ritonavir and the design of an oral solid dispersion formulation of docetaxel (ModraDoc001 10-mg capsule). Further research lead to the development of a docetaxel tablet (ModraDoc003 10-mg tablet) and a fixed-dose combination (FDC) tablet of docetaxel and ritonavir (ModraDoc004 10/50-mg tablet). In this clinical proof-of-concept study the exposure to docetaxel and ritonavir was compared between the single agent formulations and the FDC tablet. Six evaluable patients received 40 mg docetaxel and 200 mg of ritonavir once a week according to a cross-over design. No significant differences were found in the exposure to docetaxel and ritonavir between the single agent formulations and the FDC tablet. There was, however, a tendency towards a higher exposure to docetaxel after the administration of the FDC tablet, which could be an effect of the simultaneous release of docetaxel and ritonavir in the gastrointestinal tract. The FDC tablet of docetaxel and ritonavir is a pharmaceutically and clinically feasibly option in the development of patient convenient oral anti-cancer therapy with docetaxel.