{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["19(12)"],"submitter":["Toth K"],"pubmed_abstract":["<h4>Background</h4>The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors.<h4>Methods</h4>Since the prominent role in clonazepam nitro-reduction and acetylation of 7-amino-clonazepam is assigned to CYP3A and N-acetyl transferase 2 enzymes, respectively, the association between the patients' CYP3A status (CYP3A5 genotype, CYP3A4 expression) or N-acetyl transferase 2 acetylator phenotype and clonazepam metabolism (plasma concentrations of clonazepam and 7-amino-clonazepam) was evaluated in 98 psychiatric patients suffering from schizophrenia or bipolar disorders.<h4>Results</h4>The patients' CYP3A4 expression was found to be the major determinant of clonazepam plasma concentrations normalized by the dose and bodyweight (1263.5±482.9 and 558.5±202.4ng/mL per mg/kg bodyweight in low and normal expressers, respectively, P<.0001). Consequently, the dose requirement for the therapeutic concentration of clonazepam was substantially lower in low-CYP3A4 expresser patients than in normal expressers (0.029±0.011 vs 0.058±0.024mg/kg bodyweight, P<.0001). Furthermore, significantly higher (about 2-fold) plasma concentration ratio of 7-amino-clonazepam and clonazepam was observed in the patients displaying normal CYP3A4 expression and slower N-acetylation than all the others.<h4>Conclusion</h4>Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and can facilitate the improvement of personalized clonazepam therapy and withdrawal regimen."],"journal":["The international journal of neuropsychopharmacology"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5203763"],"repository":["biostudies-literature"],"pubmed_title":["Optimization of Clonazepam Therapy Adjusted to Patient's CYP3A Status and NAT2 Genotype."],"pmcid":["PMC5203763"],"pubmed_authors":["Sirok D","Monostory K","Toth K","Csukly G","Belic A","Kiss A","Hafra E","Deri M","Menus A","Bitter I"],"additional_accession":[]},"is_claimable":false,"name":"Optimization of Clonazepam Therapy Adjusted to Patient's CYP3A Status and NAT2 Genotype.","description":"<h4>Background</h4>The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors.<h4>Methods</h4>Since the prominent role in clonazepam nitro-reduction and acetylation of 7-amino-clonazepam is assigned to CYP3A and N-acetyl transferase 2 enzymes, respectively, the association between the patients' CYP3A status (CYP3A5 genotype, CYP3A4 expression) or N-acetyl transferase 2 acetylator phenotype and clonazepam metabolism (plasma concentrations of clonazepam and 7-amino-clonazepam) was evaluated in 98 psychiatric patients suffering from schizophrenia or bipolar disorders.<h4>Results</h4>The patients' CYP3A4 expression was found to be the major determinant of clonazepam plasma concentrations normalized by the dose and bodyweight (1263.5±482.9 and 558.5±202.4ng/mL per mg/kg bodyweight in low and normal expressers, respectively, P<.0001). Consequently, the dose requirement for the therapeutic concentration of clonazepam was substantially lower in low-CYP3A4 expresser patients than in normal expressers (0.029±0.011 vs 0.058±0.024mg/kg bodyweight, P<.0001). Furthermore, significantly higher (about 2-fold) plasma concentration ratio of 7-amino-clonazepam and clonazepam was observed in the patients displaying normal CYP3A4 expression and slower N-acetylation than all the others.<h4>Conclusion</h4>Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and can facilitate the improvement of personalized clonazepam therapy and withdrawal regimen.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Dec","modification":"2021-03-18T09:14:55Z","creation":"2019-03-27T02:32:53Z"},"accession":"S-EPMC5203763","cross_references":{"pubmed":["27639091"],"doi":["10.1093/ijnp/pyw083"]}}