Clinical pharmacology and metabolism of Taxol (paclitaxel): update 1993.
Paclitaxel may be one of the most important anticancer agents to be developed over the past 2 decades. With its unique mechanism of action as an inducer of tubulin assembly, paclitaxel has demonstrated impressive antitumor activity in patients with breast, lung (both non-small cell and small cell), head and neck, and advanced and platinum-refractory ovarian carcinomas. Unfortunately, there has been a relative lack of pharmacologic data available for paclitaxel, compared with other agents in similar phases of development. This scarcity of data is due, in part, to the aqueous insolubility of paclitaxel and to difficulties in developing sensitive analytic assays to measure the full range of drug concentrations achieved in small animals, both of which have limited preclinical pharmacologic studies. This report reviews the pharmacology of paclitaxel as ascertained during early clinical trials. Although most early studies used prolonged intravenous administration schedules of the agent as both monotherapy and in chemotherapy combinations, more recent studies have evaluated shorter administration schedules. In addition, available information pertaining to the pharmacodynamic and metabolic profiles of paclitaxel are discussed. Such information may be useful in designing rational treatment regimens of paclitaxel as a single agent and in chemotherapy combinations, potentially resulting in the optimal utilization of this important agent in cancer chemotherapeutics.
Rowinsky
E K
EK
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Center, Baltimore, Maryland.
Wright
M
M
Monsarrat
B
B
Donehower
R C
RC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007274:Injections, Intraperitoneal; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D017239:Paclitaxel