title: Influence of CYP3A5 polymorphism on the pharmacokinetics of psychiatric drugs.
abstract: 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.
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece. emanolop@med.duth.gr.
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000927:Anticonvulsants / Q000493:pharmacokinetics*; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A