title: A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.
abstract: 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) microg h ml(-1) and 1.97 (0.58-3.22) microg h ml(-1) after oral administration of SMEOF#3 and Taxol, respectively, and 4.69 (3.90-6.09) microg 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.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. s.veltkamp@nki.nl
authors.forename: S A
authors.initials: SA
authors.lastname: Veltkamp
authors.forename: B
authors.initials: B
authors.lastname: Thijssen
authors.forename: J S
authors.initials: JS
authors.lastname: Garrigue
authors.forename: G
authors.initials: G
authors.lastname: Lambert
authors.forename: F
authors.initials: F
authors.lastname: Lallemand
authors.forename: F
authors.initials: F
authors.lastname: Binlich
authors.forename: A D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: B
authors.initials: B
authors.lastname: Nuijen
authors.forename: A
authors.initials: A
authors.lastname: Nol
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018450:Disease Progression; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000379:methods; D045703:Emulsifying Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012449:Safety; D012995:Solubility; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D045703:Emulsifying Agents; D016572:Cyclosporine; D017239:Paclitaxel