CYP2D6 Genotyping with Oligonucleotide Microarrays and Nortriptyline Concentrations in Geriatric Depression

Murphy, Greer M.; Pollock, Bruce G.; Kirshner, Margaret A.; Pascoe, Nina; Cheuk, William; Mulsant, Benoit H.; Reynolds, Charles F.

doi:10.1016/s0893-133x(01)00289-5

Cited by 50 publications

(28 citation statements)

References 20 publications

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“…A clear relationship between 2D6 genotype and plasma concentration of nortriptyline has been documented (Murphy et al, 2001, Solai et al, 2002. Similarly, plasma concentration of paroxetine is associated with cyp2d6 genotype and venlafaxine-xr2D6 genotype at lower concentrations; at higher concentrations, paroxetine's autoinhibition of 2D6 alters that relationship (Solai et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

CYP2D6 genotype and venlafaxine‐XR concentrations in depressed elderly

Whyte

Romkes

Mulsant

et al. 2006

Int J Geriat Psychiatry

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Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

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Section: Discussionmentioning

confidence: 98%

CYP2D6 genotype and venlafaxine‐XR concentrations in depressed elderly

Whyte

Romkes

Mulsant

et al. 2006

Int J Geriat Psychiatry

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“…This concept does not differentiate between carriers of two or only one functional allele. Both are classified as EMs (predicted phenotype from genotype), despite the demonstration of a gene-dose effect in several studies (32)(33)(34)(35) and the generally accepted notion of enhanced function as a result of duplicated alleles (35 ).…”

Section: Discussionmentioning

confidence: 99%

Amitriptyline or Not, That Is the Question: Pharmacogenetic Testing of CYP2D6 and CYP2C19 Identifies Patients with Low or High Risk for Side Effects in Amitriptyline Therapy

et al. 2005

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Background: Amitriptyline has been replaced in many countries by alternative and more expensive drugs based on claims of improved tolerability and toxicity and despite slightly reduced efficacy. Preliminary studies indicate that adverse effects could be linked to polymorphisms of drug-metabolizing enzymes, but information on their clinical impact remains scanty and includes mainly case reports. We conducted a prospective blinded two-center study seeking correlations between CYP2C19 and CYP2D6 genotypes, drug concentrations, adverse events, and therapy response. Methods: Fifty Caucasian inpatients with at least medium-grade depressive disorder received amitriptyline at a fixed dose of 75 mg twice a day. Blood samples for concentration monitoring of amitriptyline and nortriptyline were taken weekly until discharge along with evaluations of depression (Hamilton Depression Scale and Clinical Global Impression Scale) and side effect (Dosage Record and Treatment Emergent Symptoms Scale; DOTES) scores. Results: In a ROC analysis, nortriptyline but not amitriptyline concentrations correlated with side effects (DOTES sum score >5; area under the curve, 0.733; P ‫؍‬ 0.008). Carriers of two functional CYP2D6 alleles had a

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“…Clinical studies must be performed in the actual clinical environment in which the pharmacogenetic test is likely to be used (17 ). Two studies have quantitatively examined the correlation between CYP2D6 gene dose (number of functional genes) and NT concentrations (35,36 ). Murphy et al (36 ) also tested for an allele with reduced function (*10), arbitrarily assigned a mutation score of 0.5 to this allele, and showed a correlation between a mutation score and NT concentrations.…”

Section: Discussion Ascoc and Fgdmentioning

confidence: 99%

Allele-Specific Change of Concentration and Functional Gene Dose for the Prediction of Steady-State Serum Concentrations of Amitriptyline and Nortriptyline in CYP2C19 and CYP2D6 Extensive and Intermediate Metabolizers

Steimer¹,

Zöpf²,

et al. 2004

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Background: Recently, new polymorphisms were described in connection with intermediate and ultrarapid CYP2D6 metabolism. These may allow a much desired prediction of metabolic activity within the extensive metabolizer group. The functional consequences are still being discussed with few data available for clinical patients. Methods: We conducted a prospective, blinded twocenter study seeking correlations between CYP2C19 (*2,*3, and *4; conventional PCR) and CYP2D6 genotypes (*1 to *10, *35, and *41; real-time and multiplex PCR) and drug concentrations (Emit ® and HPLC) in 50 Caucasians receiving amitriptyline (AT; 75 mg twice a day). Results: Eighteen CYP2C19 heterozygotes (*1/*2) had higher AT (P ‫؍‬ 0.033) and lower nortriptyline (NT; P ‫؍‬ 0.059) concentrations than 30 homozygotes (*1/*1). For CYP2D6, we calculated two new indices, i.e., the allelespecific change of concentration on identical background (ASCOC) and a quantitative functional gene

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CYP2D6 Genotyping with Oligonucleotide Microarrays and Nortriptyline Concentrations in Geriatric Depression

Abstract: Recent advances in oligonucleotide microarray technology ("gene chips")

Cited by 50 publications

References 20 publications

CYP2D6 genotype and venlafaxine‐XR concentrations in depressed elderly

CYP2D6 genotype and venlafaxine‐XR concentrations in depressed elderly

Amitriptyline or Not, That Is the Question: Pharmacogenetic Testing of CYP2D6 and CYP2C19 Identifies Patients with Low or High Risk for Side Effects in Amitriptyline Therapy

Allele-Specific Change of Concentration and Functional Gene Dose for the Prediction of Steady-State Serum Concentrations of Amitriptyline and Nortriptyline in CYP2C19 and CYP2D6 Extensive and Intermediate Metabolizers

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