氯丙咪嗪,临床注释-2,变异和临床注释数据

氯丙咪嗪

临床注释ID

1043859155

药物名称(英)

clomipramine

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

203.8125

PMID计数

计数的证据

表现型

抑郁症，重度；精神障碍

表现型(英)

Depressive Disorder, Major;Mental Disorders

最新日期

2021/4/23 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1043859155

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
666	*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 clomipramine 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 clomipramine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
665	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
664	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
663	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
662	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
661	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
660	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
659	*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 clomipramine 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 clomipramine 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 clomipramine as compared to patients with other alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.
658	*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 clomipramine 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 clomipramine 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 clomipramine 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 clomipramine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence metabolism of clomipramine.

临床证据

id	证据的ID	总结
1058	1448631815	CYP2D6 4/41 is associated with increased trough concentration of clomipramine and desmethyl clomipramine.
1057	1450368707	CYP2D6 4/5 is associated with decreased metabolism of clomipramine.
1056	1446903175	CYP2D6 3 + 4 + 5 + 6 are not associated with concentrations of clomipramine in people with Mental Disorders as compared to CYP2D6 1/1.
1055	1446901471	CYP2D6 1/1xN is associated with decreased concentrations of clomipramine in people with Depression.
1054	1446901449	CYP2D6 4/6 is associated with increased concentrations of clomipramine in people with Depressive Disorder, Major.
1053	1446901329	CYP2D6 2/1xN is associated with decreased concentrations of clomipramine in people with Agoraphobia.
1052	1183616923	CYP2D6 4/5 is associated with increased clomipramine and desmethyl clomipramine plasma concentration when treated with clomipramine in people with Depressive Disorder, Major as compared to CYP2D6 *1.
1051	1183616915	CYP2D6 3/4 is associated with increased clomipramine and desmethyl clomipramine plasma concentration when treated with clomipramine in people with Depressive Disorder, Major as compared to CYP2D6 *1.
1050	1183616907	CYP2D6 3/4 (assigned as poor metabolizers phenotype) is associated with decreased clearance of clomipramine in healthy individuals as compared to CYP2D6 *1 (assigned as normal metabolizers phenotype) .
1049	1183616898	CYP2D6 4/5 (assigned as poor metabolizers phenotype) is associated with decreased clearance of clomipramine in healthy individuals as compared to CYP2D6 *1 (assigned as normal metabolizers phenotype) .
1048	1183616668	CYP2D6 4/4 is associated with increased clomipramine and desmethyl clomipramine plasma concentration when treated with clomipramine in people with Depressive Disorder, Major as compared to CYP2D6 *1.
1047	1183616635	CYP2D6 4/4 (assigned as poor metabolizers phenotype) is associated with decreased clearance of clomipramine in healthy individuals as compared to CYP2D6 *1 (assigned as normal metabolizers phenotype) .
1046	982030030	CYP2D6 10/10 is not associated with difference in the metabolic ratio of desmethyl clomipramine (DC)/hydroxy desmethyl clomipramine (HDC) when treated with clomipramine in people with Mental Disorders as compared to CYP2D6 1/1.
1045	1184470662	CYP2D6 poor metabolizers are associated with increased plasma concentrations of clomipramine and desmethylclomipramine when treated with clomipramine.
1044	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.
1043	1183683968	CYP2D6 poor metabolizer is associated with increased plasma concentrations of clomipramine and desmethylclomipramine when treated with clomipramine.
1042	1183683963	CYP2D6 poor metabolizer is associated with decreased metabolism of clomipramine in people with Depressive Disorder, Major as compared to CYP2D6 normal metabolizers.
1041	PA166104964	Annotation of DPWG Guideline for clomipramine and CYP2D6
1040	PA166105007	Annotation of CPIC Guideline for clomipramine and CYP2C19, CYP2D6

临床病史

id	类型	评论
901	Update	Added DPWG guideline as evidence
900	Update	CA score added as part of scoring system release. LOE assigned following curator review.
899	Update	changed to allele description and PK evidence only
898	Update	Corrected typo and reworded some phenotype descriptions.
897	Update

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