Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients.
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| Title: | Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients. |
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| Authors: | Schenk, P. W., van Fessem, M. A. C., Verploegh-Van Rij, S., Mathot, R. A. A., van Gelder, T., Vulto, A. G., van Vliet, M., Lindemans, J., Bruijn, J. A., van Schaik, R. H. N. |
| Source: | Molecular Psychiatry. Jun2008, Vol. 13 Issue 6, p597-605. 9p. 2 Charts, 3 Graphs. |
| Subjects: | Mental health, Genetic polymorphisms, Genetic research, Drug therapy, Drug side effects |
| Abstract: | The inactivation and clearance of the tricyclic antidepressant imipramine is dependent on CYP2D6 activity. First, CYP2C19 converts imipramine into the active metabolite desipramine, which is then inactivated by CYP2D6. This retrospective single center study aimed to prove whether CYP2C19 and ample CYP2D6 genotyping (taking into consideration four null alleles and three decreased-activity alleles) could be used to predict imipramine and desipramine plasma concentrations in depressed patients, and whether genotype-based drug dose recommendations might assist in the early management of imipramine pharmacotherapy. In 181 subjects with major depressive disorder, drug doses were recorded, imipramine and desipramine plasma concentrations were monitored and CYP2C19 (*2) and CYP2D6 genotype (*3, *4, *5, *6, *9, *10, *41 and gene duplication) were obtained, yielding graded allele-specific CYP2D6 patient groups. Desipramine and imipramine+desipramine plasma concentration per drug dose unit, imipramine dose at steady state, and imipramine dose requirement significantly depended on CYP2D6 genotype (Kruskal–Wallis test, P<0.0001). Mean (±s.d.) drug dose requirements were 131 (±109), 155 (±70), 217 (±95), 245 (±125), 326 (±213), and 509 (±292) mg imipramine/day in carriers of 0, 0.5, 1, 1.5, 2, and >2 active CYP2D6 genes, respectively. Our protocol for CYP2D6 genotyping will thus importantly aid in the prediction of imipramine metabolism, allowing for the use of an adjusted starting dose and faster achievement of predefined imipramine+desipramine plasma levels in all genetic patient subgroups. Therefore, therapeutic efficacy and efficiency may be improved, the number of adverse drug reactions decreased, and hospital stay reduced.Molecular Psychiatry (2008) 13, 597–605; doi:10.1038/sj.mp.4002057; published online 31 July 2007 [ABSTRACT FROM AUTHOR] |
| Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 32066461 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Schenk%2C+P%2E+W%2E%22">Schenk, P. W.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Fessem%2C+M%2E+A%2E+C%2E%22">van Fessem, M. A. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Verploegh-Van+Rij%2C+S%2E%22">Verploegh-Van Rij, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Mathot%2C+R%2E+A%2E+A%2E%22">Mathot, R. A. A.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Gelder%2C+T%2E%22">van Gelder, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Vulto%2C+A%2E+G%2E%22">Vulto, A. G.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Vliet%2C+M%2E%22">van Vliet, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Lindemans%2C+J%2E%22">Lindemans, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Bruijn%2C+J%2E+A%2E%22">Bruijn, J. A.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Schaik%2C+R%2E+H%2E+N%2E%22">van Schaik, R. H. N.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Jun2008, Vol. 13 Issue 6, p597-605. 9p. 2 Charts, 3 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Mental+health%22">Mental health</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+research%22">Genetic research</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+therapy%22">Drug therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+side+effects%22">Drug side effects</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The inactivation and clearance of the tricyclic antidepressant imipramine is dependent on CYP2D6 activity. First, CYP2C19 converts imipramine into the active metabolite desipramine, which is then inactivated by CYP2D6. This retrospective single center study aimed to prove whether CYP2C19 and ample CYP2D6 genotyping (taking into consideration four null alleles and three decreased-activity alleles) could be used to predict imipramine and desipramine plasma concentrations in depressed patients, and whether genotype-based drug dose recommendations might assist in the early management of imipramine pharmacotherapy. In 181 subjects with major depressive disorder, drug doses were recorded, imipramine and desipramine plasma concentrations were monitored and CYP2C19 (*2) and CYP2D6 genotype (*3, *4, *5, *6, *9, *10, *41 and gene duplication) were obtained, yielding graded allele-specific CYP2D6 patient groups. Desipramine and imipramine+desipramine plasma concentration per drug dose unit, imipramine dose at steady state, and imipramine dose requirement significantly depended on CYP2D6 genotype (Kruskal–Wallis test, P<0.0001). Mean (±s.d.) drug dose requirements were 131 (±109), 155 (±70), 217 (±95), 245 (±125), 326 (±213), and 509 (±292) mg imipramine/day in carriers of 0, 0.5, 1, 1.5, 2, and >2 active CYP2D6 genes, respectively. Our protocol for CYP2D6 genotyping will thus importantly aid in the prediction of imipramine metabolism, allowing for the use of an adjusted starting dose and faster achievement of predefined imipramine+desipramine plasma levels in all genetic patient subgroups. Therefore, therapeutic efficacy and efficiency may be improved, the number of adverse drug reactions decreased, and hospital stay reduced.Molecular Psychiatry (2008) 13, 597–605; doi:10.1038/sj.mp.4002057; published online 31 July 2007 [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/sj.mp.4002057 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 597 Subjects: – SubjectFull: Mental health Type: general – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Genetic research Type: general – SubjectFull: Drug therapy Type: general – SubjectFull: Drug side effects Type: general Titles: – TitleFull: Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Schenk, P. W. – PersonEntity: Name: NameFull: van Fessem, M. A. C. – PersonEntity: Name: NameFull: Verploegh-Van Rij, S. – PersonEntity: Name: NameFull: Mathot, R. A. A. – PersonEntity: Name: NameFull: van Gelder, T. – PersonEntity: Name: NameFull: Vulto, A. G. – PersonEntity: Name: NameFull: van Vliet, M. – PersonEntity: Name: NameFull: Lindemans, J. – PersonEntity: Name: NameFull: Bruijn, J. A. – PersonEntity: Name: NameFull: van Schaik, R. H. N. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2008 Type: published Y: 2008 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 13 – Type: issue Value: 6 Titles: – TitleFull: Molecular Psychiatry Type: main |
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