多虑平,临床注释-2,变异和临床注释数据

多虑平

临床注释ID

1043859430

药物名称(英)

doxepin

变异单倍型

CYP2D6*1, CYP2D6*1xN, CYP2D6*2xN, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*9, CYP2D6*10, CYP2D6*35, CYP2D6*35xN, 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

216.125

PMID计数

计数的证据

表现型

表现型(英)

最新日期

2021/4/23 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1043859430

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
685	*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 doxepin 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 doxepin as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
684	*35xN	The CYP2D635xN alleles (1x2 and 1x鈮?) have been assigned as increased function alleles by CPIC. Patients carrying a CYP2D635xN 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 doxepin as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a CYP2D635xN 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 doxepin as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a CYP2D635xN 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 doxepin as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
683	*35	The CYP2D635 allele is assigned as a normal function allele by CPIC. Patients carrying the CYP2D635 allele in combination with alleles that result in a normal metabolizer phenotype may have increased metabolism of doxepin 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 CYP2D635 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of doxepin 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 CYP2D635 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of doxepin 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. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
682	*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 doxepin 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 doxepin 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 doxepin 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 doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
681	*9	The CYP2D69 allele is assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the CYP2D69 allele in combination with a no or decreased function allele may have decreased metabolism of doxepin as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the CYP2D6*9 allele in combination with an increased function allele may have increased metabolism of doxepin as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
680	*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 doxepin 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 doxepin 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 doxepin 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 doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
679	*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 doxepin 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 doxepin 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 doxepin 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 doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
678	*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 doxepin 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 doxepin 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 doxepin 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 doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
677	*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 doxepin 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 doxepin 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 doxepin as compared to patients with other alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
676	*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 doxepin 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 doxepin 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 doxepin as compared to patients with other alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.
675	*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 doxepin 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 doxepin 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 doxepin 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. This annotation only covers the pharmacokinetic relationship between CYP2D6 and doxepin and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of doxepin.

临床证据

id	证据的ID	总结
664	1446905772	CYP2D6 1xN/9 + 1xN/10 + 1xN/41 + 2xN/41 + 1xN/1 + 2xN/1 + 1xN/35 + 2xN/35 + 35xN/1 are associated with increased metabolism of doxepin in healthy individuals as compared to CYP2D6 1/1 + 1/2 + 1/35 + 1/9 + 1/10 + 2/41 + 35/41.
663	1446905879	CYP2D6 4/4 + 3/5 + 4/5 are associated with decreased metabolism of doxepin in healthy individuals as compared to CYP2D6 1/1.
662	1446905682	CYP2D6 3/4 is associated with decreased metabolism of doxepin.
661	1183622858	CYP2D6 2xN/35 is associated with decreased AUC of the sum of doxepin and N-desmethyldoxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1 + 1/2.
660	1183622848	CYP2D6 35/1xN is associated with decreased AUC of the sum of doxepin and N-desmethyldoxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1 + 1/2.
659	1183622800	CYP2D6 2xN/1 is associated with decreased AUC of the sum of doxepin and N-desmethyldoxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1 + 1/2.
658	1183617426	CYP2D6 4/4 is associated with decreased dose of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline or Opipramol in people with Depression as compared to CYP2D6 1/1.
657	1183617418	CYP2D6 4/4 is associated with increased risk of Side Effects when treated with amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline or Opipramol in people with Depression as compared to CYP2D6 1/1.
656	982030125	CYP2D6 1/1xN is associated with decreased AUC of the sum of doxepin and N-desmethyldoxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1 + 1/2.
655	982030093	CYP2D6 3/5 is associated with decreased median oral clearance of doxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1.
654	982030087	CYP2D6 4/5 is associated with decreased median oral clearance of doxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1.
653	982030079	CYP2D6 4/4 is associated with decreased median oral clearance of doxepin when treated with doxepin in healthy individuals as compared to CYP2D6 1/1.
652	1446900301	CYP2D6 poor metabolizers are associated with decreased metabolism of doxepin in human liver microsomes as compared to CYP2D6 normal metabolizers.
651	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.
650	PA166104994	Annotation of DPWG Guideline for doxepin and CYP2D6
649	PA166105000	Annotation of CPIC Guideline for doxepin and CYP2C19, CYP2D6

临床病史

id	类型	评论
928	Update	Added DPWG guideline as evidence
927	Update	CA score added as part of scoring system release. LOE assigned following curator review.
926	Update	changed to allele description and PK evidence only
925	Update	Added PMID 11037801 to evidence and updated phenotype descriptions
924	Update	Updated OMB race to appropriate biogeographical group
923	Update	added " or 1/2" to 1/1xN and 1/*2xN annotations

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