Predicting Paclitaxel Disposition in Humans With Whole-Body Physiologically-Based Pharmacokinetic Modeling.

ABSTRACT: Paclitaxel is a commonly used drug in the treatment of multiple solid tumors, including cancers of the breast, lung, and ovaries. Despite the established exposure-pharmacodynamic relationships for paclitaxel, treatment is associated with wide interindividual pharmacokinetic variability that leads to unpredictability of the agent's clinical activity and toxicity. We hypothesized that physiologically-based modeling approaches could be employed to predict the human pharmacokinetics of paclitaxel following administration of the approved Cremophor-based formulation (Taxol). The model was developed from tissue distribution studies performed in mice and applied to plasma concentration-time data obtained in adult cancer patients receiving Taxol at the approved dose and schedule (175 mg/m2 by a 3-h

SUBMITTER: Fu Q 

PROVIDER: S-EPMC6930855 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature