CYP2C19 variation and citalopram response
| Autor: | Dennis J. O'Kane, Maureen S. Drews, David A. Mrazek, Richard M. Weinshilboum, Karen Snyder, Julie M. Cunningham, Joanna M. Biernacka, A. J. Rush, Susanna R. Stevens, John L. Black |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male CYP2D6 medicine.medical_specialty Adolescent CYP2C19 Citalopram Biology Polymorphism Single Nucleotide Article Young Adult Gene Frequency Internal medicine Genetics medicine Humans General Pharmacology Toxicology and Pharmaceutics Young adult Molecular Biology Allele frequency Genetic Association Studies Genetics (clinical) Aged CYP3A4 Depression Remission Induction Genetic Variation Drug Tolerance Middle Aged Cytochrome P-450 CYP2C19 Treatment Outcome Endocrinology Pharmacogenomics Antidepressive Agents Second-Generation Molecular Medicine Female Aryl Hydrocarbon Hydroxylases Algorithms Pharmacogenetics medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 21:1-9 |
| ISSN: | 1744-6872 |
| DOI: | 10.1097/fpc.0b013e328340bc5a |
| Popis: | Objective Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. Methods The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n= 1074). Results Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P = 0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P = 0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P = 0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. Conclusion Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram. |
| Databáze: | OpenAIRE |
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