A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer

To explore the parmacokinetics, safety and tolerability of paclitaxel after oral administration of SMEOF#3, a novel Self-Microemulsifying Oily Formulation, in combination with cyclosporin A (CsA) in patients with advanced cancer. Seven patients were enrolled and randomly assigned to receive oral paclitaxel (SMEOF#3) 160 mg+CsA 700 mg on day 1, followed by oral paclitaxel (Taxol (R)) 160 mg + CsA 700 mg on day 8 (group I) or vice versa (group II). Patients received paclitaxel (Taxol (R)) 160 mg as 3-h infusion on day 15. The median ( range) area under the plasma concentration-time curve of paclitaxel was 2.06 (1.15-3.47) mu g h ml(-1) and 1.97 (0.58-3.22) mu g h ml(-1) after oral administration of SMEOF#3 and Taxol (R), respectively, and 4.69 (3.90-6.09) mu g h ml(-1) after intravenous Taxol (R). Oral SMEOF#3 resulted in a lower median T-max of 2.0 (0.5-2.0) h than orally applied Taxol (R) (T-max=4.0 (0.8-6.1) h, P=0.02). The median apparent bioavailability of paclitaxel was 40 (19-83)% and 55 (9-70)% for the oral SMEOF#3 and oral Taxol (R) formulation, respectively. Oral paclitaxel administered as SMEOF#3 or Taxol (R) was safe and well tolerated by the patients. Remarkably, the SMEOF#3 formulation resulted in a significantly lower Tmax than orally applied Taxol (R), probably due to the excipients in the SMEOF#3 formulation resulting in a higher absorption rate of paclitaxel.