阿米替林,临床注释-2,变异和临床注释数据

阿米替林

临床注释ID

1183617651

药物名称(英)

amitriptyline

变异单倍型

CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, CYP2D6*41

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

213

PMID计数

计数的证据

表现型

抑郁症；精神障碍

表现型(英)

Depressive Disorder;Mental Disorders

最新日期

2021/4/23 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1183617651

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
737	*41	The CYP2D641 allele is assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the CYP2D641 allele in combination with a no or decreased function allele may have decreased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*41 allele in combination with an increased function allele may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
736	*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 amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*10 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
735	*6	The CYP2D66 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D63 allele in combination with alleles that result in intermediate or poor metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*6 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
734	*5	The CYP2D65 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D65 allele in combination with alleles that result in intermediate or poor metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*5 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
733	*4	The CYP2D64 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D64 allele in combination with alleles that result in intermediate or poor metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*4 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
732	*3	The CYP2D63 allele is assigned as a no function allele by CPIC. Patients carrying the CYP2D63 allele in combination with alleles that result in intermediate or poor metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*3 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
731	*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 amitriptyline as compared to patients with a combination of alleles that result in intermediate or poor metabolizer phenotype. Patients carrying the CYP2D6*2 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with a combination of alleles that result in ultrarapid metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
730	*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 amitriptyline 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 amitriptyline 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 amitriptyline as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.
729	*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 amitriptyline as compared to patients with a combination of alleles that result in intermediate or poor metabolizer phenotype. Patients carrying the CYP2D6*1 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of amitriptyline as compared to patients with a combination of alleles that result in ultrarapid metabolizer phenotype. However, conflicting evidence has been reported. This annotation only covers the pharmacokinetic relationship between CYP2D6 and amitriptyline and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of amitriptyline.

临床证据

id	证据的ID	总结
5244	1446903489	CYP2D6 4/4 is not associated with metabolism of amitriptyline as compared to CYP2D6 normal metabolizers.
5243	1446903345	CYP2D6 4/5 + 4/4 are associated with decreased metabolism of amitriptyline as compared to CYP2D6 9 + 10 + 1 + 2.
5242	1446903324	CYP2D6 4/4 is associated with increased concentrations of amitriptyline.
5241	1446903079	CYP2D6 3 + 4 + 5 + 6 are associated with increased concentrations of nortriptyline in people with Mental Disorders as compared to CYP2D6 1/1.
5240	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.
5239	1183623082	CYP2D6 4/4 is associated with decreased clearance of amitriptyline in one suicide case.
5238	1183617206	CYP2D6 5/10 + 10/10 is associated with increased ratio of nortriptyline and its metabolite (NT/EHNT) when treated with amitriptyline in people with Mental Disorders as compared to CYP2D6 1/1 + 1/2.
5237	1183617193	CYP2D6 2/5 + 1/10 is not associated with differences in the ratio of nortriptyline and its metabolite when treated with amitriptyline in people with Mental Disorders as compared to CYP2D6 1/1 + 1/2.
5236	1183615397	CYP2D6 4/4 is associated with increased amitriptyline/(E)-10- OH-AT ratio when treated with amitriptyline as compared to CYP2D6 *1.
5235	1183615381	CYP2D6 4/4 is associated with increased nortriptyline/(E)-10-OH-NT ratio when treated with amitriptyline as compared to CYP2D6 *1.
5234	1183615357	CYP2D6 4/4 is associated with increased amitriptyline + nortriptyline plasma concentration in one CYP2D6 PM when treated with amitriptyline.
356	827777570	CYP2D6 41 is associated with increased plasma nortriptyline when treated with amitriptyline in people with Mental Disorders as compared to CYP2D6 1.
355	827777575	CYP2D6 10 is associated with increased plasma nortiptyline when treated with amitriptyline in people with Mental Disorders as compared to CYP2D6 1.
354	827777562	CYP2D6 4 is associated with increased plasma nortiptyline when treated with amitriptyline in people with Mental Disorders as compared to CYP2D6 1.
353	1446901646	CYP2D6 poor metabolizers are associated with decreased metabolism of amitriptyline in people with Depression as compared to CYP2D6 normal metabolizers.
352	1446901072	CYP2D6 poor metabolizers are associated with decreased metabolism of amitriptyline in healthy individuals as compared to CYP2D6 normal metabolizers.
351	1183684300	CYP2D6 poor metabolizers is associated with increased antidepressant serum levels when treated with amitriptyline, clomipramine, doxepin, imipramine or trimipramine in people with Mental Disorders as compared to CYP2D6 normal metabolizers.
350	PA166104982	Annotation of DPWG Guideline for amitriptyline and CYP2D6
349	PA166105006	Annotation of CPIC Guideline for amitriptyline and CYP2C19, CYP2D6

临床病史

id	类型	评论
1019	Update	Added DPWG guideline as evidence
1018	Update	CA score added as part of scoring system release. LOE assigned following curator review.
1017	Update	Updated text to follow template. Added sections for 1xN and 2
1016	Update	Attached CPIC guideline and removed override. Altered text slightly. Added conflicting evidence statement.
1015	Note	This is companion annotation to 1448999816. This annotation contains the alleles with CPIC functions and high level of evidence whereas 1448999816 has the uncertain function alleles and lower level of evidence.
1014	Update	split evidence into PK and ADR

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