Mechanisms of Physiological Changes in Drug Exposure in Cancer Patients
Cancer is the second most common cause of death in the USA, surpassed only by heart disease, and is a significant focus of pharmaceutical research and development. Oncology drugs are often toxic which often precludes conducting clinical trials in healthy volunteers. Therefore, getting new treatments quickly and safely to patients is essential.
Cancer patients differ from healthy individuals in terms of their demographics and physiology. These changes mean that the pharmacokinetics of drugs may be altered in this population compared to healthy volunteers. Furthermore, cancer patients often take multiple medications concurrently to treat comorbidities and treatment-associated side effects. Therefore, patients face an increased risk of drug-drug interactions (DDIs) for which drug label guidance is essential. For all these reasons, there is significant interest in using a virtual oncology population to aid mechanistic physiologically-based pharmacokinetic (PBPK) modelling of cancer drugs. Furthermore, a PBPK cancer population is a useful platform for investigating tumor disposition and therefore, impact on treatment regimens. It also enables conducting virtual DDI trials to assess the potential for safety concerns.
- Physiological considerations in cancer patients
- Building virtual cancer patient populations
- Application of mechanistic PBPK to explain differences in drug disposition
- Case studies of approved drugs oncology drugs
- Utilization of the permeability-limited tumor model compartment to predict intercellular concentrations