CYP2D6 polymorphism

CYP2D6 [polymorphisms] (MIM 124030) Slow metabolism of certain drugs (eg, debrisoquin), resulting in their accumulation... 

Mendoza, R., Wan, Y. J. etal. (2001).CYP2D6 polymorphism in aMexican American population. Clin. Pharmacol. Ther., 70(6), 552-60. 

Casner, P. (2005). The effect of CYP2D6 polymorphisms on dextromethorphan metabolism in Mexican Americans. /. Clin. Pharmacol., 45, 1230-5. 

Risperidone and its active metabolite 9-OH-resperidone are metabolized by CYP2D6. Polymorphic metabolism should be considered in those with side effects at low doses (approximately 40% of African Americans and Asians can have increased side effects from risperidone and other drugs metabolized through CYP2D6). 

CerviUa, J.A., Russ, C., Holmes, C., et al. (1999) CYP2D6 polymorphisms in Alzheimer s disease, with and without extrapyramidal signs, showing no apolipoprotein E epsilon 4 effect modification. Biol. Psychiatry, 45, 426-429. 

Furuno, T., Kawanishi, C., Iseki, E., et al. (2001) No evidence of an association between CYP2D6 polymorphisms among Japanese and dementia with Lewy bodies. Psychiatry Clin. Neurosci., 55, 89-92. 

Varsaldi, F., MigUo, G., Scordo, M.G., et al. (2006) Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer s disease patients. Eur. J. Clin. Pharmacol., 62, 721-726. 

Elevations of TCA levels may occur when combined with CYP2D6 inhibitors or from constitutional factors. About 7% of the Caucasian population in the USA has a CYP2D6 polymorphism that is associated with slow metabolism of TCAs and other 2D6 substrates. Combination of a known CYP2D6 inhibitor and a TCA in a patient who is a slow metabolizer may result in additive effects. Such an interaction has been implicated, though rarely, in cases of TCA toxicity. There may also be additive TCA effects such as anticholinergic or antihistamine effects when combined with other agents that share these properties such as benztropine or diphenhydramine. Similarly, antihypertensive drugs may exacerbate the orthostatic hypotension induced by TCAs. 

Ellingrod VL, Miller D, Schultz SK, Wehring H, Arndt S. CYP2D6 polymorphisms and atypical antipsychotic weight gain. Psychiatr Genet 2002 12(l) 55-8. 

Unexpected neurotoxicity from amphetamine and its analogs (e.g. 3,4 methylenedioxymethamphetamine, also known as ecstasy ) as well as interactions with other drugs subject to CYP2D6 polymorphism would likewise be expected to occur more frequently among Africans and Caucasians than in Asians.(112)... 

Brynne N, Dalen P, Alvan G, Bertilsson L, Gabrielsson J. The influence of CYP2D6 polymorphism on the pharmacokinetics and dynamics of tolterodine. Clin Pharmacol Ther 1998 63 529-539. 

Brynne N. Consequences of CYP2D6 Polymorphism for the Disposition and Dynamics of Tolterodine. Ph.D. dissertation, Karolinska Institutet, Stockholm, 1998. 

Thieme D, Rolf B, Sachs H et al (2008) Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms. Int J Legal Med 122 149-155... 

Actually, CY2D6 gene polymorphisms, associated with null or reduced enzyme activity, have been reported to negatively influence (in a gene-dose manner) the blood level of endoxifen in numerous prospective pharmacokinetic studies [11,172, 192-196], Some retrospective and prospective studies have shown that CYP2D6 polymorphism was associated with worse clinical outcomes in PMs and IMs patients in terms of recurrence and disease free survival or BC development in the chemo-prevention setting [192,194,195,197-205],... 

Schroth W et al (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 302 1429-1436... 

Ramon y Cajal T et al (2010) Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment. Breast Cancer Res Treat 119 33-38... 

It was the identification of a group of subjects unable to metabolize debrisoquine (118,119), resulting in a potentially life-threatening drop in blood pressure, which lead to the identification of the CYP2D6 polymorphism (120). Debrisoquine is metabolized specifically by CYP2D6 (121) to produce 4-hydroxy debrisoquine. 

Capon DA, Bochner F, Kerry N, et al. The influence of CYP2D6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans. Clin Pharmacol Ther 1996 60 295-307. 

Al-Hadidi HF, Irshaid YM, Rawashdeh NM. Metoprolol alpha-hydroxylation is a poor probe for debrisoquine oxidation (CYP2D6) polymorphism in Jordanians. Eur J Clin Pharmacol 1994 47 311-314. 

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