Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions
- PMID:18537577
- DOI: 10.2174/138920008784746373
Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions
Abstract
The involvement of cytochrome P450 (CYP) enzymes in the metabolism of the atypical (second-generation) antipsychotics clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and amisulpride is reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4; the 9-hydroxy metabolite of risperidone (paliperidone) is now marketed as an antipsychotic in its own right. Olanzapine is metabolized primarily by direct glucuronidation and CYP1A2 and to a lesser extent by CYP2D6 and CYP3A4. Quetiapine is metabolized by CYP3A4, as is ziprasidone, although in the latter case aldehyde oxidase is the enzyme responsible for most of the metabolism. CYP2D6 and CYP3A4 are important in the metabolism of aripiprazole, and CYP-catalyzed metabolism of paliperidone and amisulpride appears to be minor. At the usual clinical doses, these drugs appear to not generally affect markedly the metabolism of other coadministered medications. However, as indicated above, several of atypical antipsychotics are metabolized by CYP enzymes, and physicians should be aware of coadministered drugs that may inhibit or induce these CYP enzymes; examples of such possible interactions are presented in this review.
Similar articles
- Interactions between the cytochrome P450 system and the second-generation antipsychotics.Prior TI, Baker GB.Prior TI, et al.J Psychiatry Neurosci. 2003 Mar;28(2):99-112.J Psychiatry Neurosci. 2003.PMID:12670127Free PMC article.Review.
- Drug metabolism and atypical antipsychotics.Prior TI, Chue PS, Tibbo P, Baker GB.Prior TI, et al.Eur Neuropsychopharmacol. 1999 Jun;9(4):301-9. doi: 10.1016/s0924-977x(98)00040-6.Eur Neuropsychopharmacol. 1999.PMID:10422890Review.
- Metabolic drug interactions with newer antipsychotics: a comparative review.Spina E, de Leon J.Spina E, et al.Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):4-22. doi: 10.1111/j.1742-7843.2007.00017.x.Basic Clin Pharmacol Toxicol. 2007.PMID:17214606Review.
- Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions.Prakash C, Kamel A, Cui D, Whalen RD, Miceli JJ, Tweedie D.Prakash C, et al.Br J Clin Pharmacol. 2000;49 Suppl 1(Suppl 1):35S-42S. doi: 10.1046/j.1365-2125.2000.00151.x.Br J Clin Pharmacol. 2000.PMID:10771452Free PMC article.
- Metabolic drug interactions with new psychotropic agents.Spina E, Scordo MG, D'Arrigo C.Spina E, et al.Fundam Clin Pharmacol. 2003 Oct;17(5):517-38. doi: 10.1046/j.1472-8206.2003.00193.x.Fundam Clin Pharmacol. 2003.PMID:14703714Review.
Cited by
- Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products.Chesney E, McGuire P, Freeman TP, Strang J, Englund A.Chesney E, et al.Ther Adv Psychopharmacol. 2020 Sep 9;10:2045125320954992. doi: 10.1177/2045125320954992. eCollection 2020.Ther Adv Psychopharmacol. 2020.PMID:32973998Free PMC article.Review.
- Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients.Aquino A, Alexandrino GL, Guest PC, Augusto F, Gomes AF, Murgu M, Steiner J, Martins-de-Souza D.Aquino A, et al.Front Psychiatry. 2018 May 25;9:209. doi: 10.3389/fpsyt.2018.00209. eCollection 2018.Front Psychiatry. 2018.PMID:29887809Free PMC article.
- The association of genetic polymorphisms in CYP1A2, UGT1A4, and ABCB1 with autonomic nervous system dysfunction in schizophrenia patients treated with olanzapine.Hattori S, Suda A, Miyauchi M, Shiraishi Y, Saeki T, Fukushima T, Fujibayashi M, Tsujita N, Ishii C, Ishii N, Moritani T, Saigusa Y, Kishida I.Hattori S, et al.BMC Psychiatry. 2020 Feb 18;20(1):72. doi: 10.1186/s12888-020-02492-5.BMC Psychiatry. 2020.PMID:32070304Free PMC article.
- Severe potential drug-drug interactions in older adults with dementia and associated factors.Bogetti-Salazar M, González-González C, Juárez-Cedillo T, Sánchez-García S, Rosas-Carrasco O.Bogetti-Salazar M, et al.Clinics (Sao Paulo). 2016 Jan;71(1):17-21. doi: 10.6061/clinics/2016(01)04.Clinics (Sao Paulo). 2016.PMID:26872079Free PMC article.
- Pharmacogenetics in the Treatment of Huntington's Disease: Review and Future Perspectives.García-González X, Cubo E, Simón-Vicente L, Mariscal N, Alcaraz R, Aguado L, Rivadeneyra-Posadas J, Sanz-Solas A, Saiz-Rodríguez M.García-González X, et al.J Pers Med. 2023 Feb 22;13(3):385. doi: 10.3390/jpm13030385.J Pers Med. 2023.PMID:36983567Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources