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^®) 160 mg+CsA 700 mg on day 8 (group I) or vice versa (group II). Patients received paclitaxel (Taxol^®) 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) μg h ml⁻¹ and 1.97 (0.58–3.22) μg h ml⁻¹ after oral administration of SMEOF#3 and Taxol^®, respectively, and 4.69 (3.90–6.09) μg h ml⁻¹ after intravenous Taxol^®. Oral SMEOF#3 resulted in a lower median T_max of 2.0 (0.5–2.0) h than orally applied Taxol^® (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^® formulation, respectively. Oral paclitaxel administered as SMEOF#3 or Taxol^® was safe and well tolerated by the patients. Remarkably, the SMEOF#3 formulation resulted in a significantly lower T_max than orally applied Taxol^®, probably due to the excipients in the SMEOF#3 formulation resulting in a higher absorption rate of paclitaxel.British Journal of Cancer (2006) 95, 729–734. doi:10.1038/sj.bjc.6603312 www.bjcancer.com Published online 22 August 2006 [ABSTRACT FROM AUTHOR]