阿立哌唑,临床注释-2,变异和临床注释数据

阿立哌唑

临床注释ID

1183619068

药物名称(英)

aripiprazole

变异单倍型

CYP2D6*1, 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

105.875

PMID计数

计数的证据

表现型

精神障碍；分裂情感障碍；精神分裂症

表现型(英)

Psychotic Disorders;schizoaffective disorder;Schizophrenia

最新日期

2021/10/19 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1183619068

专业人口(英)

专业人口

临床等位基因

id	等位基因	注释文本
642	*41	The CYP2D641 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 41 allele in combination with a decreased or no function allele may have decreased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *41 allele in combination with an increased function allele may have increased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. Other genetic and clinical factors may also influence aripiprazole metabolism. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes.
641	*10	The CYP2D610 allele has been assigned as a decreased function allele with an activity value of 0.25 by CPIC. Patients carrying the 10 allele in combination with a decreased or no function allele may have decreased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 10 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 10 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. Other genetic and clinical factors may also influence aripiprazole metabolism. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes.
640	*6	The CYP2D66 allele has been assigned as a no function allele by CPIC. Patients carrying the 6 allele in combination with a decreased, normal or no function allele may have decreased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 6 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 6 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence aripiprazole metabolism.
639	*5	The CYP2D65 allele has been assigned as a no function allele by CPIC. Patients carrying the 5 allele in combination with a decreased, normal or no function allele may have decreased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 5 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 5 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence aripiprazole metabolism.
638	*4	The CYP2D64 allele has been assigned as a no function allele by CPIC. Patients carrying the 4 allele in combination with a decreased, normal or no function allele may have decreased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 4 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 4 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of aripiprazole as compared to patients with alleles that result in a normal metabolizer phenotype. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence aripiprazole metabolism.
637	*1	The CYP2D61 allele is assigned as a normal function allele by CPIC. Patients carrying the 1 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of aripiprazole as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele. Patients carrying the *1 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of aripiprazole as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a decreased or no function allele but increased metabolism of aripiprazole as compared to patients with a no function allele in combination with a decreased or normal function allele or two decreased or no function alleles. Be aware that the DPWG guideline for aripiprazole and CYP2D6 has a 'no recommendation' for CYP2D6 ultrarapid and intermediate metabolizers. This annotation only covers the pharmacokinetic relationship between CYP2D6 and aripiprazole and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence aripiprazole metabolism.

临床证据

id	证据的ID	总结
1013	1451548640	CYP2D6 3 + 4 + 4xN + 5 + 6 + 10 + 41 are associated with increased concentrations of aripiprazole as compared to CYP2D6 1 + *1xN.
1012	1183697486	CYP2D6 1/1 + 1/10 (assigned as normal metabolizer phenotype) are associated with decreased metabolism of aripiprazole in healthy individuals also being given paroxetine as compared to CYP2D6 10/10 + 10/21 (assigned as intermediate metabolizer phenotype) .
1011	1183618864	CYP2D6 5 + 10 + 41 is associated with decreased metabolism of aripiprazole in healthy individuals as compared to CYP2D6 1.
1010	1183618626	CYP2D6 4 + 5 + 6 is associated with decreased metabolism of aripiprazole as compared to CYP2D6 1.
1009	1183697499	CYP2D6 1/1 + 1/10 + 1/21 + 1/5 (assigned as normal metabolizer phenotype) are not associated with decreased metabolism of aripiprazole in healthy individuals also being given fluvoxamine as compared to CYP2D6 10/10 + 5/10 (assigned as intermediate metabolizer phenotype) .
1008	1183618939	CYP2D6 2 is not associated with decreased metabolism of aripiprazole in healthy individuals as compared to CYP2D6 1.
1007	1451251861	CYP2D6 intermediate metabolizer phenotype is associated with decreased metabolism of aripiprazole as compared to genotypes 1/3 + 1/4 + 1/5 + 1/6 (assigned as intermediate metabolizer phenotype) .
1006	1448993561	CYP2D6 poor metabolizer genotype is associated with increased dose-adjusted trough concentrations of aripiprazole in people with Psychotic Disorders as compared to CYP2D6 normal metabolizer genotype.
1005	1447682087	CYP2D6 poor metabolizer is associated with decreased metabolism of aripiprazole in people with schizoaffective disorder or Schizophrenia as compared to CYP2D6 normal metabolizer.
1004	1183906189	CYP2D6 intermediate metabolizers is not associated with serum concentration of dehydroaripiprazole when treated with aripiprazole as compared to CYP2D6 1/3 + 1/4 + 1/5 + 1/6.
1003	PA166104937	Annotation of DPWG Guideline for aripiprazole and CYP2D6

临床病史

id	类型	评论
873	Update	Added PMID 30604050 to evidence
872	Update	Checked.
871	Update	Added DPWG guideline and updated text to LOE 1A template. CA requires independent curator check before approval.
870	Update	CA score added as part of scoring system release. LOE may have automatically changed based on new score but may be subject to further changes upon curator review.
869	Update	only PK evidence

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