CYP2D6

Cytochroma P450 CYP2D6 (-atis, n.) (Numerus EC: 1.14.14.1) est haemoproteinum et pars gregis Cytochroma P450 ideo in metabolismo medicamentorum inter centesimae vicenas et quinas vicenas interest. Huic cytochromati polymorphismus exstat, ideo plures phaenotypi cum variis activitatibus noti sunt.^[1]

Cave: notitiae huius paginae nec praescriptiones nec consilia medica sunt.

Natura structuraque biochemica

Cytochroma P450 CYP2D6 est et polypeptidum et haemoproteinum, quod ex 497 acidis aminicis constitutum est.

Genetica

Phaenotypicae variantia

Pluribus variantiis geni CYP2D6 (chromosoma 22q13.1) varietates phaenotypicae sequuntur. Activitates igitur enzymaticae discriptae sunt^[2]^[3]

tarda ("poor metabolizer") — functio nulla seu laesa
intermedia ("intermediate metabolizer")
extensiva ("extensive metabolizer") sive efficiens ("efficient metabolizer") — functionis normalis apte dicens
rapida ("ultrarapid metabolizer") — pluria CYP2D6 genorum expressa sunt ex quibus functio aucta nascitur (polymorphismus geneticus)

Allelonorum variantia

Allelonorum^[4] quoque variantia CYP2D6 allelo chromosomatis 22 explicabilis est quae plures quam centum allela continet.

CYP2D6 enzymi activitas for selected alles
αλλήλων	CYP2D6 activitas
CYP2D61*	normalis
CYP2D62*	normalis
CYP2D63*	nulla
CYP2D64*	nulla
CYP2D65*	nulla
CYP2D66*	nulla
CYP2D67*	nulla
CYP2D68*	nulla
CYP2D69*	laesa
CYP2D610*	laesa
CYP2D611*	nulla
CYP2D612*	nulla
CYP2D613*	nulla
CYP2D614*	nulla
CYP2D615*	nulla
CYP2D617*	laesa
CYP2D619*	nulla
CYP2D620*	nulla
CYP2D621*	nulla
CYP2D629*	laesa
CYP2D631*	nulla
CYP2D638*	nulla
CYP2D640*	nulla
CYP2D641*	laesa
CYP2D642*	nulla
CYP2D668*	nulla
CYP2D692*	nulla
CYP2D6100*	nulla
CYP2D6101*	nulla
CYP2D6 duplicatio	aucta

Pharmaca ad CYP2D6 relata

Substrati	Inhibitores^[7]	Inductores^[8]
Pharmaca relata ad CYP2D6^[5]^[6].
Antiarrhythmica (classis I) Flecainidum Lidocaínum Propafenonum Encainidum Mexiletinum Substantiae beta-receptoria inhibendi Propranololum^[9] Metoprololum Carvedilolum^[10] Timololum Alprenololum Atenololum Bisoprololum^[11] ( (R)-(+)-bisoprololum > (S)-(-)-bisoprololum) ) Substantiae antidepressivae Antidepressiva tricyclica Imipraminum Amitriptylinum Doxepinum Antidepressiva tetracyclica Mianserinum Mirtazapinum^[12] Inhibitores reabsorptionis Serotonini selectivi (SSRI) Fluoxetinum Paroxetinum Venlafaxinum Opioidi Codeinum Tramadolum Oxicodonum Debrisoquinum Dextrometorphanum Antipsychotica Haloperidolum Risperidonum Perphenazinum Thioridazinum Zuclopenthixolum Remoxipridum Aripiprazolum Ondansetronum Fenforminum Tropisetronum Amphetamina Chlorfenaminum Tamoxifenum Cinnarizidum^[13] Flunarizidum	Substantiae beta-receptoria inhibendi Metoclopramidum Inhibitores reabsorptionis Serotonini selectivi (SSRI): Citalopramum Fluoxetinum (forte) Paroxetinum (forte) Moclobemidum Terbinaphinum Quinidinum Amiodaronum Alia antidepressiva Clomipraminum Doxepinum Antibiotica Ciprofloxacinum Antihistaminica Chlorphenaminum Difenhidraminum Antipsychotica Pimozidum Thioridazinum Chlorpromazinum^[14] Haloperidolum Melperonum^[15]^[16]^[17] Perphenazinum Zuclopenthixolum Bupropionum (forte) Celecoxibum Cimetidinum Chloranphenicolum Cocaina Doxorubicinum Metoclopramidum Metadonum Moclobemidum Quinidinum Ranitidinum Ranolazinum Ritonavirum Halophantrinum Imipraminum Levomepromazinum Vincae alcaloidi^[18] Aimalicinum Berberinum Coniinum Ergotaminum Graminum Harmalinum Laudanosinum Sempervirinum Vinblastinum Vincaminum Vincristinum Chinidinum (forte) Dimenhydrinatum	Piperidinum Gluthetimidum (forte) Carbamazepinum Dexametasonum Rifampicinum Propafenonum

Exempli gratia aegrotus quidam Paroxetinum (inhibitorem reabsorptionis Serotonini selectivum, inhibitorem CYP2D6) simul cum Metoprololo (Substantia beta-receptoria inhibendi, substrato CYP2D6) consumens a causa de Paroxetini inhibitione demonstrare effectus secundarios potest. Istud potissimum φάρμακον^[19] vigilantiae est.

Cancer mammae

Ad cancri therapiam mammae substratum CYP2D6 tamoxifenum uti potest. Posse aegrotas in depressionem quoque incidere et simul se cum inhibitoribus CYP2D6 antidepressivis, per exemplum paroxetino, tractari notum est. Haec combinatio substrati cum inhibitore ad debilitationem tamoxifeni effectuum ducere potest.^[20]

Notae

↑ Ingelman-Sundberg M (2005). Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenom J 5: 6-13
↑ Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A (2002). Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 53 (2): 111–22.
↑ Llerena A, Dorado P, Peñas-Lledó EM (2009). Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics. 10 (1): 17–28
↑ Verbum de αλλήλων, allelon, alleli n. derivatum
↑ Cozza KL, Armstrong SC (2001). The Cytochrome P450 System. Drug Interaction Principles for Medical Practice. Washington, DC: American Psychiatric Publishing
↑ Preskorn SH (1996). Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. 1st ed.: Professional Communications, Inc.
↑ Inhibitor cum subtratorum effectibus fortioribus
↑ Inductor cum subtratorum effectibus minoribus
↑ substratum quoque CYP1A2 (solum gregum chemicorum lateralium)
↑ substratum quoque CYP2C9
↑ Yuji Horikiri; Takehiko Suzuki; Masakazu Mizobe (March 1998). "Pharmacokinetics and metabolism of bisoprolol enantiomers in humans". Journal of Pharmaceutical Sciences 87 (3): 289–294
↑ Lind AB, Reis M, Bengtsson F, Jonzier-Perey M, Powell Golay K, Ahlner J, Baumann P, Dahl ML (2009). "Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour". Clin Pharmacokinet 48 (1): 63-70
↑ Narimatsu S., Kariya S., Isozaki S., Ohmori S., Kitada M., Hosokawa S., Masubuchi Y., Suzuki T. (Iun 1993). "Involvement of CYP2D6 in oxidative metabolism of cinnarizine and flunarizine in human liver microsomes". Biochemical and biophysical research communications 193 (3): 1262-8 doi:10.1006/bbrc.1993.1761
↑ Acute dyskinetic syndrome during chloropromazine treatment of a female patient with CYP2D6 poor metabolism phenotype
↑ Gahr, M; Gastl, R; Kölle, MA; Schönfeldt-Lecuona, C; Freudenmann, RW (2012). "Successful treatment of schizophrenia with melperone augmentation in a patient with phenotypic CYP2D6 ultrarapid metabolization: a case report". Journal of Medical Case Reports 6 (1): 49 (Anglice)
↑ Köhnke, MD; Lutz, U; Wiatr, G; Schwärzler, F; Weller, B; Schott, K; Buchkremer, G (April 2006). "Cytochrome P450 2D6 dependent metabolization of risperidone is inhibited by melperone". European Journal of Clinical Pharmacology 62 (4): 333–334 (Anglice)
↑ Grözinger, M; Dragicevic, A; Hiemke, C; Shams, M; Müller, MJ; Härtter, S (January 2003). "Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine". Pharmacopsychiatry 36 (1): 3–6 (Anglice)
↑ Tabula subtratorum inhibitorum cytochromatis CYP2D6, fons: Ingelman-Sundberg M: Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity, The Pharmacogenomics Journal (Anglice)
↑ pharmacon = Genitivus pluralis: eo φάρμακον vigilantia significat remediorum sive medicamentorum vigilantia
↑ Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study (Serotoni inhibitores et cancri mammae mortalitas feminarum cum uso tamoxifeni) (Anglice)

Nexus externi

PharmGKB: explanatae PGx genorum informationes ad CYP2D6 (Anglice)

[Ingelman_2005-1] Ingelman-Sundberg M (2005). Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenom J 5: 6-13

[2] Bertilsson L, Dahl ML, Dalén P, Al-Shurbaji A (2002). Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 53 (2): 111–22.

[3] Llerena A, Dorado P, Peñas-Lledó EM (2009). Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics. 10 (1): 17–28

[4] Verbum de αλλήλων, allelon, alleli n. derivatum

[5] Cozza KL, Armstrong SC (2001). The Cytochrome P450 System. Drug Interaction Principles for Medical Practice. Washington, DC: American Psychiatric Publishing

[6] Preskorn SH (1996). Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. 1st ed.: Professional Communications, Inc.

[7] Inhibitor cum subtratorum effectibus fortioribus

[8] Inductor cum subtratorum effectibus minoribus

[Q_CYP1A2-9] substratum quoque CYP1A2 (solum gregum chemicorum lateralium)

[Q_CYP2C9-10] substratum quoque CYP2C9

[11] Yuji Horikiri; Takehiko Suzuki; Masakazu Mizobe (March 1998). "Pharmacokinetics and metabolism of bisoprolol enantiomers in humans". Journal of Pharmaceutical Sciences 87 (3): 289–294

[12] Lind AB, Reis M, Bengtsson F, Jonzier-Perey M, Powell Golay K, Ahlner J, Baumann P, Dahl ML (2009). "Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour". Clin Pharmacokinet 48 (1): 63-70

[13] Narimatsu S., Kariya S., Isozaki S., Ohmori S., Kitada M., Hosokawa S., Masubuchi Y., Suzuki T. (Iun 1993). "Involvement of CYP2D6 in oxidative metabolism of cinnarizine and flunarizine in human liver microsomes". Biochemical and biophysical research communications 193 (3): 1262-8 doi:10.1006/bbrc.1993.1761

[14] Acute dyskinetic syndrome during chloropromazine treatment of a female patient with CYP2D6 poor metabolism phenotype

[15] Gahr, M; Gastl, R; Kölle, MA; Schönfeldt-Lecuona, C; Freudenmann, RW (2012). "Successful treatment of schizophrenia with melperone augmentation in a patient with phenotypic CYP2D6 ultrarapid metabolization: a case report". Journal of Medical Case Reports 6 (1): 49 (Anglice)

[16] Köhnke, MD; Lutz, U; Wiatr, G; Schwärzler, F; Weller, B; Schott, K; Buchkremer, G (April 2006). "Cytochrome P450 2D6 dependent metabolization of risperidone is inhibited by melperone". European Journal of Clinical Pharmacology 62 (4): 333–334 (Anglice)

[17] Grözinger, M; Dragicevic, A; Hiemke, C; Shams, M; Müller, MJ; Härtter, S (January 2003). "Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine". Pharmacopsychiatry 36 (1): 3–6 (Anglice)

[INGELMAN_TAB-18] Tabula subtratorum inhibitorum cytochromatis CYP2D6, fons: Ingelman-Sundberg M: Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity, The Pharmacogenomics Journal (Anglice)

[19] rmacon = Genitivus pluralis: eo φάρμακον vigilantia significat remediorum sive medicamentorum vigilantia

[20] Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study (Serotoni inhibitores et cancri mammae mortalitas feminarum cum uso tamoxifeni) (Anglice)

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