Influence of CYP3A5 polymorphism on the pharmacokinetics of psychiatric drugs

Background: The contribution of the CYP3A5 enzyme to the metabolism of clinically used drugs has been established only for a few CYP3A substrates, such as the immunosuppressant tacrolimus, while for drugs used in the field of psychiatry its role is still vague. Methods: We herein discuss all published data on the contribution of CYP3A5 and its polymorphisms to the metabolism of antipsychotics and antidepressants that are known to be metabolized by CYP3A enzymes, as well as of carbamazepine, an antiepileptic drug used as mood stabilizer. Published papers from 1990 to April 2015 were retrieved from PubMed and Scopus by use of the keywords CYP3A5, CYP3A, gene polymorphism, antipsychotics, psychiatry, pharmacogenomics, haloperidol, risperidone, quetiapine, aripiprazole, clozapine, olanzapine, antidepressants, and carbamazepine. Results: Available evidence is only sparse and no firm conclusions can be drawn on whether CYP3A5 enzyme exhibits affinity and metabolic capacity similar to CYP3A4 for these drugs. Nevertheless, the role of CYP3A5 should be studied further, since there is evidence suggesting that CYP3A5 potentially catalyses alternative metabolic pathways that may give rise to intermediate metabolites with yet unknown pharmacologic properties and may also limit drug bioavailability through intestinal first pass metabolism. Additionally, expression of CYP3A5 may overcome CYP3A4 drug-drug interactions. Conclusions: Overall, CYP3A5 is an overlooked polymorphic enzyme and its potential in improving psychiatric pharmacogenomics remains to be explored. The impact of CYP3A5 pharmacogenetics in the clinical setting merits the attention of both researchers and clinicians.