Heterogeneity in drug disposition determines interindividual variability of docetaxel pharmacokinetics.

摘要

Cytochrome P450 (CYP) is involved in the metabolism of a variety of anticancer dn with CYP3A being the most abundant enzyme expressed in the human liver and intestin CYP activities can be modified by several factors including genetic polymorphisms' environmental factors such as smoking, changes in physiological conditions such as age and disease status, and drug-drug or drug-food interactions. These factors may cause interindividual differences in the pharmacokinetic (PK) profiles of anticancer agents leading to variations in dtug efficacy and/or toxicity. A classical example is the pharmacokinetic profile of docetaxel, which is characterized by substantial interindividual variability in systemic drug exposure (AUC) and drug clearance that is largely due to the catalytic function of CYP3A involved in the metabolism and elimination of the drug. As such understanding the mechanisms responsible for differences in drug disposition factors affecting the variability in drug clearance and response is an area of intense investigation.