Paclitaxel

This chapter introduces paclitaxel and describes its prepration methods, physical properties, analysis methods, stability, pharmacokinetics, and metabolism. Paclitaxel is an antineoplastic agent that is highly effective against ovarian and breast cancer. The different methods for paclitaxel preparations that include old extraction method, new extraction method, semisynthetic method (cell culture-based method), total paclitaxel synthesis method (Holton's method, Nicolaou's method, and Danishefsky's method) are discussed in the chapter. Paclitaxel is highly lipophilic and practically insoluble in water. It is reported to be stable over 24 h at a concentration of 0.3–1.2 mg/ml. Paclitaxel exhibit many toxic effects, which arise from the drug itself or from the diluting vehicle used in the formulation. Various clinical trials are carried out to evaluate the activity of paclitaxel, and the results of these studies are summarized in the chapter. The drug interaction shows that paclitaxel is metabolized by hepatic cytochrome P-450 enzymes, particularly isoenzymes 3A and 2C. When administered with other drugs, altered metabolism is expected, which depends on the target molecule, schedule, and sequence of administration. Some of the interactions include decrease in the clearance of paclitaxel when paclitaxel was administered after cisplatin. Myelosuppression is more severe when paclitaxel precedes cyclophosphamide.