Intravenous-to-oral switch in anticancer chemotherapy: a focus on docetaxel and paclitaxel.
Oral administration of the taxanes docetaxel and paclitaxel is hampered by their affinity for drug transporters, especially ABCB1 (P-glycoprotein, Pgp); extensive first-pass metabolism by cytochrome P450 3A (CYP3A); and poor drug solubility. Preclinical studies in Pgp-deficient and wild-type mice demonstrated that modulation of either Pgp or CYP3A resulted in high systemic exposure to docetaxel or paclitaxel. This concept could successfully be translated to clinical trials.
Koolen
S L W
SL
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands.
Beijnen
J H
JH
Schellens
J H M
JH
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000077143:Docetaxel; D006801:Humans; D007262:Infusions, Intravenous; D017239:Paclitaxel / Q000008:administration & dosage* / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage* / Q000378:metabolism
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D051544:Cytochrome P-450 CYP3A; D017239:Paclitaxel