Investigational New Drugs

, Volume 19, Issue 2, pp 155–162 | Cite as

Oral Delivery of Taxanes

  • Mirte M. Malingré
  • Jos H. Beijnen
  • Jan H.M. Schellens


Oral treatment with cytotoxic agents is tobe preferred as this administration routeis convenient to patients, reducesadministration costs and facilitates theuse of more chronic treatment regimens. Forthe taxanes paclitaxel and docetaxel,however, low oral bioavailability haslimited development of treatment by theoral route. Preclinical studies with mdr1aP-glycoprotein knock-out mice, which lackfunctional P-glycoprotein activity in thegut, have shown significant bioavailabilityof orally administered paclitaxel.Additional studies in wild-type micerevealed good bioavailability after oraladministration when paclitaxel was combinedwith P-glycoprotein blockers such ascyclosporin A or the structurally relatedcompound SDZ PSC 833. Based on theextensive preclinical research, thefeasibility of oral administration ofpaclitaxel and docetaxel in cancer patientswas recently demonstrated in our Institute.Co-administration of cyclosporin A stronglyenhanced the oral bioavailability of bothpaclitaxel and docetaxel. For docetaxel incombination with cyclosporin A an oralbioavailability of 90% was achieved withan interpatient variability similar to thatafter intravenous drug administration; forpaclitaxel the oral bioavailability isestimated at approximately 50%. The safety of the oralroute for both taxanes is good. A phase IIstudy of weekly oral docetaxel incombination with cyclosporin A is currentlyongoing.

paclitaxel docetaxel oral administration bioavailability P-glycoprotein cytochrome P450 


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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Mirte M. Malingré
    • 1
    • 2
  • Jos H. Beijnen
    • 1
    • 2
    • 3
  • Jan H.M. Schellens
    • 1
    • 3
  1. 1.Department of Medical OncologyThe Netherlands Cancer Institute/Antoni van Leeuwenhoek HospitalThe Netherlands
  2. 2.Department of Pharmacy and PharmacologyThe Netherlands Cancer Institute/Slotervaart HospitalAmsterdamThe Netherlands
  3. 3.Division of Drug Toxicology, Faculty of PharmacyUtrecht UniversityUtrechtThe Netherlands

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