Alterations of chemotherapeutic pharmacokinetic profiles by drug-drug interactions

作者：Mani Sridhar^*; Ghalib Mohammed; Chaudhary Imran; Goel Sanjay

来源：Expert Opinion on Drug Metabolism and Toxicology, 2009, 5(2): 109-130.

DOI：10.1517/17425250902753212

• drug metabolism
• orphan nuclear receptors
• pharmacokinetic-pharmacodynamic relationships
• pregnane X receptor
• transcriptional regulation

Background: Drug interactions in oncology are common place and largely ignored as we tolerate high thresholds of 'toxic' drug responses in these patients. However, in the era of 'targeted' or seemingly 'less toxic' therapy, these interactions are more commonly flagged and contribute significantly towards poor 'quality of life' and medical fatalities. Objective: This review and opinion article focuses on alteration of chemotherapeutic pharmacokinetic profiles by drug interactions in the setting of polypharmacy. The assumption is that the drugs, with changes in their pharmacokinetics, will contribute towards changes in their pharmacodynamics. Methods: The examples cited for such drug-drug interactions are culled from published literature with an emphasis on those interactions that have been well characterized at the molecular level. Results: Although very few drug interaction studies have been performed on approved oncology based drugs, it is clear that drugs whose pharmacokinetics profiles are closely related to their pharmacodynamics will indeed result in clinically important drug interactions. Some newer mechanisms are described that involve interactions at the level of gene transcription, whereby, drug metabolism is significantly altered. However, for any given drug interaction, there does not seem to be a comprehensive model describing interactions. Conclusions: Mechanisms based drug interactions are plentiful in oncology, however, there is an absolute lack of a comprehensive model that would predict drug-drug interactions.

• 出版日期2009-2