Clinical Pharmacology – Chemical
2019 PharmSci 360
Inflammatory disease-induced changes in drug clearance can result in increased variability in drug exposure and increase the challenge to the prescribing physician to predictably dose patients within the therapeutic window.
There is growing understanding that inflammatory disease can increase cytokine production leading to down-regulation of cytochrome P450 (CYP) enzymes, conjugative enzymes, or transporters. This presentation will briefly review the theory of how cancer can lead to indirect changes in CYP-mediated drug metabolism, review acute phase proteins and cytokines as markers of changes in CYP activity in cancer patients, and provide clinical case examples of how the inflammation in advanced cancer patients can lead to altered CYP3A4-mediated drug clearance. Finally, recent data will be presented to compare the inflammatory effects of cancer on drug-mediated clearance to that of other inflammatory diseases.