Drug-Drug Interactions (DDIs) in Psychiatric Practice, Part 3: Pharmacokinetic Considerations

This column is the third in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first column in this series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs and how to recognize such DDIs, and strategies for avoiding them. The second column in the series further discussed strategies for avoiding and/or minimizing adverse outcomes from DDIs. This third column deals with pharmacokinetic considerations concerning DDIs in psychiatric practice. Specifically, this column discusses the 2 major types of pharmacokinetically mediated DDIs: those mediated by cytochrome P450 (CYP) enzymes and those mediated by transport proteins. The role of each of these regulatory proteins in the pharmacokinetics of drugs is reviewed as well as how genetically determined variation in the functional activity of these regulatory proteins can alter the accumulation of a drug in the body (ie, via CYP enzymes) and in specific compartments of the body (ie, via transport proteins), either increasing or decreasing their accumulation leading to either reduced efficacy or increased toxicity. This column further explains how coprescribed drugs can also affect the functional integrity of these regulatory proteins and lead to differences from usual in the accumulation of drugs dependent on the activity of these CYP enzymes and drug transporters. This phenomenon is known as phenoconversion in which a patient can functionally change from his or her genetic status, for example, having extensive or normal metabolism, to having poor or slow metabolism and hence greater accumulation than would be expected based on the patient's genotype.