Docetaxel differs from paclitaxel in two positions in

its chemical structure and this small check details alteration makes it more watersoluble. Taxanes disrupt microtubule dynamics by stabilizing the microtubule against depolymerization, enhancing their polymerization, promoting the nucleation and elongation phases of the polymerization reaction, and reducing the critical tubulin subunit concentration required Inhibitors,research,lifescience,medical for microtubule assembly. Moreover they alter the tubulin dissociation rate at both ends of the microtubule. This leads to reduced dynamic instability, whereas the association rate is not affected. After the treatment with taxanes, the microtubules Inhibitors,research,lifescience,medical are highly stable and resistant to depolymerization by cold, calcium ions, dilution, and other antimicrotubule agents. The final result is the impairment of dynamics of microtubule depolymerization, which is a critical event in the mitotic process [5]. Paclitaxel is active against primary epithelial ovarian carcinoma, breast cancer, colon, non-small-cell lung cancer, and AIDS-related Kaposi’s sarcoma in preclinical models Inhibitors,research,lifescience,medical [3, 6, 7] and is presently of common use in the treatment of several important malignancies as

lung cancer, breast cancer, Kaposi’s sarcoma, squamous cell carcinoma of the head and neck, gastric cancer, esophageal cancer, bladder cancer, and other carcinomas. Despite being clinically very active, paclitaxel and docetaxel are associated with many serious sideeffects which often preclude the prolonged use in patients. A number

of these Inhibitors,research,lifescience,medical side effects have been associated with the vehicles used for the formulation: the cremophor EL (CrEL-polyethoxylated castor oil) [8] for paclitaxel and polysorbate 80 (Tween 80) for Inhibitors,research,lifescience,medical docetaxel, respectively, that altered also their pharmacokinetic profiles; CrEL is considered to be responsible for the hypersensitivity reactions seen in patients during paclitaxel therapy. In vitro, CrEL caused L-NAME HCl axonal swelling, demyelination, and axonal degeneration, and, thus, it may also contribute to the development of neuropathy in patients receiving paclitaxel. The use of CrEL requires premedication with antihistamines and corticosteroids to prevent hypersensitivity reactions and, despite these premedications, approximately 40% of all patients will have minor reactions (e.g., flushing and rash) and 3% will have life threatening reactions. CrEL also causes leaching of the plasticizers from polyvinyl chloride (PVC) bags and infusions sets; thus paclitaxel must be infused via the use of special non-PVC infusion systems and in-line filtration. Another effect induced by CrEL is the alteration of lipoprotein pattern and the consequent hyperlipidemia.