去甲替林,临床注释-2,变异和临床注释数据

去甲替林

临床注释ID

1183618725

药物名称(英)

nortriptyline

变异单倍型

CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*2xN, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, CYP2D6*17

基因

CYP2D6

证据级别

水平覆盖

水平修饰符

Tier 1 VIP

表现型类别(英)

Metabolism/PK

表现型类别

代谢/PK

分数

228.375

PMID计数

计数的证据

表现型

抑郁症，主要

表现型(英)

Depressive Disorder, Major

最新日期

2021/4/23 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1183618725

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
922	*17	The CYP2D617 allele is assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the CYP2D617 allele in combination with a no or decreased function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*17 allele in combination with an increased function allele may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
921	*10	The CYP2D610 allele is assigned as a decreased function allele with an activity value of 0.25 by CPIC. Patients carrying the CYP2D610 allele in combination with a no or decreased function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D610 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the CYP2D610 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
920	*6	The CYP2D66 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D66 allele in combination with a no, decreased or normal function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D66 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the CYP2D66 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
919	*5	The CYP2D65 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D65 allele in combination with a no, decreased or normal function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D65 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the CYP2D65 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
918	*4	The CYP2D64 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D64 allele in combination with a no, decreased or normal function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D64 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the CYP2D64 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
917	*3	The CYP2D63 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D63 allele in combination with a no, decreased or normal function allele may have decreased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D63 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the CYP2D63 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
916	*2xN	The CYP2D62xN alleles (1x2 and 1x鈮?) have been assigned as increased function alleles by CPIC. Patients carrying a CYP2D62xN allele in combination with a normal or increased function allele or a decreased function allele with an activity value of 0.5 may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a CYP2D62xN allele with an activity value of 3 or greater in combination with a decreased function allele with an activity value of 0.25 or a no function allele may also have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a CYP2D62xN allele with an activity value of 2 in combination with a decreased function allele with an activity value of 0.25 or a no function allele may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
915	*2	The CYP2D62 allele is assigned as a normal function allele by CPIC. Patients carrying the CYP2D62 allele in combination with alleles that result in a normal metabolizer phenotype may have increased metabolism of nortriptyline as compared to patients with a no function allele in combination with a decreased or normal function allele or two no or decreased function alleles. Patients carrying the CYP2D62 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of nortriptyline as compared to patients with an increased function allele in combination with an increased or normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the CYP2D62 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of nortriptyline as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele with an activity value of 0.25. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
914	*1xN	The CYP2D61xN alleles (1x2 and 1x鈮?) have been assigned as increased function alleles by CPIC. Patients carrying a CYP2D61xN allele in combination with a normal or increased function allele or a decreased function allele with an activity value of 0.5 may have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a CYP2D61xN allele with an activity value of 3 or greater in combination with a decreased function allele with an activity value of 0.25 or a no function allele may also have increased metabolism of nortriptyline as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a CYP2D61xN allele with an activity value of 2 in combination with a decreased function allele with an activity value of 0.25 or a no function allele may have similar metabolism of nortriptyline as compared to patients with other alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.
913	*1	The CYP2D61 allele is assigned as a normal function allele by CPIC. Patients carrying the CYP2D61 allele in combination with alleles that result in a normal metabolizer phenotype may have increased metabolism of nortriptyline as compared to patients with a no function allele in combination with a decreased or normal function allele or two no or decreased function alleles. Patients carrying the CYP2D61 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of nortriptyline as compared to patients with an increased function allele in combination with an increased or normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the CYP2D61 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of nortriptyline as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele with an activity value of 0.25. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and nortriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of nortriptyline.

临床证据

id	证据的ID	总结
3471	1183624207	CYP2D6 1/4 + 1/5 is not associated with differences in nortriptyline concentrations when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1.
3470	1183618505	CYP2D6 5 is associated with increased nortriptyline concentrations corrected for dose and weight when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1 + 1/*2.
3469	1183618467	CYP2D6 10 is associated with increased nortriptyline concentrations corrected for dose and weight when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1 + 1/*2.
3468	1183618387	CYP2D6 5/10 is associated with increased mean nortriptyline concentrations and nortriptyline concentrations per unit dose of the medication when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1.
3467	1183618379	CYP2D6 3 is associated with increased mean nortriptyline concentrations and nortriptyline concentrations per unit dose of the medication when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/*1.
3466	1183618362	CYP2D6 4 is associated with increased mean nortriptyline concentrations and nortriptyline concentrations per unit dose of the medication when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/*1.
3465	1183618249	CYP2D6 4/4 is associated with decreased maximum plasma concentration of 10-hydroxy nortriptyline when exposed to nortriptyline in healthy individuals as compared to CYP2D6 1/1.
3464	1183618241	CYP2D6 1/2xN is associated with increased maximum plasma concentration of 10-hydroxy nortriptyline when exposed to nortriptyline in healthy individuals as compared to CYP2D6 1/1.
3463	1183618233	CYP2D6 5 is associated with increased apparent terminal elimination half-life when exposed to nortriptyline in healthy individuals as compared to CYP2D6 1/*1.
3462	1183618225	CYP2D6 3 is associated with increased apparent terminal elimination half-life when exposed to nortriptyline in healthy individuals as compared to CYP2D6 1/*1.
3461	1183618214	CYP2D6 4 is associated with increased apparent terminal elimination half-life when exposed to nortriptyline in healthy individuals as compared to CYP2D6 1/*1.
3460	1447519884	CYP2D6 ultrarapid metabolizer phenotype are associated with increased metabolism of nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 normal metabolizers.
3459	1447519878	CYP2D6 intermediate metabolizers are associated with decreased metabolism of nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 normal metabolizers.
3458	1446901165	CYP2D6 poor metabolizers are associated with increased concentrations of nortriptyline in people with Depressive Disorder, Major.
3457	1446900047	CYP2D6 ultrarapid metabolizer phenotype is associated with increased metabolism of nortriptyline in people with Depressive Disorder, Major.
3456	1183698887	CYP2D6 poor metabolizers are associated with decreased metabolism of nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 normal metabolizers.
3455	PA166104961	Annotation of DPWG Guideline for nortriptyline and CYP2D6
3454	PA166104998	Annotation of CPIC Guideline for nortriptyline and CYP2D6
2775	1446904494	CYP2D6 4/4 + 1/4 + 1/5 are associated with decreased metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1 + 1/2xN.
2774	1446904458	CYP2D6 2/2 + 2/10 + 1/3 + 1/4 + 2/4 + 5/10 + 4/4 + 3/4 are associated with increased concentrations of nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/2 + 1/10 + 1/1.
2773	1446904319	CYP2D6 2/1xN is associated with increased dose of nortriptyline in people with Depressive Disorder, Major.
2772	1446903079	CYP2D6 3 + 4 + 5 + 6 are associated with increased concentrations of nortriptyline in people with Mental Disorders as compared to CYP2D6 1/1.
2771	1446902725	CYP2D6 1/4 + 2/4 + 2/5 + 4/41 + 4/10 are associated with increased concentrations of nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1 + 1/2 + 2/1xN + 2/2 + 1/41 + 1/10 + 2/41.
2770	1446901389	CYP2D6 2/1xN is associated with increased metabolism of nortriptyline in people with Depressive Disorder, Major.
2769	1446899759	CYP2D6 1/10 is not associated with decreased metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1.
2768	1184468865	CYP2D6 5/10 is associated with increased plasma concentrations when treated with nortriptyline.
2767	1184468543	CYP2D6 10/10 is associated with decreased metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1 + 1/10.
2766	1184468532	CYP2D6 1/10 is not associated with metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1.
2765	1184468498	CYP2D6 10/10 is associated with decreased metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1.
2764	1184468489	CYP2D6 1/10 is not associated with metabolism of nortriptyline in healthy individuals as compared to CYP2D6 1/1.
2763	1183678570	CYP2D6 17 is associated with decreased clearance of nortriptyline as compared to CYP2D6 1.
2762	1183678562	CYP2D6 10 is associated with decreased clearance of nortriptyline as compared to CYP2D6 1.
2761	1183624247	CYP2D6 1/1xN is associated with very low nortriptyline after 7 days of treatment when treated with nortriptyline.
2760	1183624218	CYP2D6 1/4 + 1/5 is associated with decreased concentrations of 10-OH-nortriptyline and higher nortriptyline/10-OH-nortriptyline ratio when treated with nortriptyline in people with Depressive Disorder, Major as compared to CYP2D6 1/1.

临床病史

id	类型	评论
625	Update	Added DPWG guideline as evidence
624	Update	CA score added as part of scoring system release. LOE assigned following curator review.
623	Update	modified to allele level description and PK evidence only

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