Review : Pharmacokinetics and pharmacodynamics of the taxanes

Abstract

Objectives. To review the pharmacokinetics and pharmacodynamics of docetaxel and paclitaxel. Data Sources. We reviewed the literature through a MEDLINE search from 1982 to 1996. The terms docetaxel, paclitaxel, taxanes, and taxoids were used in the search. Relevant articles cited in literature obtained by MEDLINE searching, as well as new articles published in early 1997 in specific oncology journals, were also considered. Data Extraction. We have reviewed the current literature with regard to the chemistry, mechanisms of action and pharmacology, pharmacokinetics, clini cal use, adverse effects, drug interactions, formula tion, dosage, administration, and pharmaceutical is sues of the taxanes. Conclusion. Both docetaxel and paclitaxel are novel antineoplastic agents with significant activity in many types of cancer. The pharmacokinetics of both agents are best characterized by a three-compartment disposition profile. However, the pharmacokinetics of paclitaxel, not docetaxel, are non-linear and can be described by a saturation process in distribution and elimination. The nonlinearity appears to be associated more frequently with shorter infusions and/or higher doses. There is evidence suggesting that the time duration of paclitaxel concentrations maintained above 0.1 μM/L (T>0.1 μM ) is associated with improved survival and development of toxicity. On the other hand, currently there is no information relating opti mal systemic exposure of docetaxel to efficacy and toxicity. In addition, these pharmacokinetic-pharma codynamic relationship may change with therapy with antineoplastic agents and other agents adminis tered concurrently, and necessitates additional phar macokinetic-pharmacodynamic investigations.