曲马多,临床注释,变异和临床注释数据

曲马多

临床注释ID

1451155020

药物名称(英)

tramadol

变异单倍型

CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*9, CYP2D6*10, CYP2D6*17, 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

227.1875

PMID计数

计数的证据

表现型

表现型(英)

最新日期

2021-10-28

URL

https://www.pharmgkb.org/clinicalAnnotation/1451155020

专业人口(英)

Pediatric

专业人口

儿科

临床等位基因

id	等位基因	注释文本
118	*41	The CYP2D641 allele has been assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the 41 allele in combination with a decreased or no function allele may have decreased metabolism of tramadol 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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
117	*17	The CYP2D617 allele has been assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the 17 allele in combination with a decreased or no function allele may have decreased metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *17 allele in combination with an increased function allele may have increased metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
116	*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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 10 allele in combination with a normal function allele or an increased function allele with an activity value of 2 may have similar metabolism of tramadol 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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
115	*9	The CYP2D69 allele has been assigned as a decreased function allele with an activity value of 0.5 by CPIC. Patients carrying the 9 allele in combination with a normal, decreased or no function allele may have decreased metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *9 allele in combination with an increased function allele may have increased metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
114	*6	The CYP2D66 allele has been assigned as a no function allele by CPIC. Patients carrying the 6 allele in combination with with a decreased, normal or no function allele may have decreased metabolism of tramadol 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 tramadol 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 tramadol 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 tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
113	*5	The CYP2D65 allele has been assigned as a no function allele by CPIC. Patients carrying the 5 allele in combination with with a decreased, normal or no function allele may have decreased metabolism of tramadol 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 tramadol 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 tramadol 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 tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
112	*4	The CYP2D64 allele has been assigned as a no function allele by CPIC. Patients carrying the 4 allele in combination with with a decreased, normal or no function allele may have decreased metabolism of tramadol 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 tramadol 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 tramadol 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 tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
111	*3	The CYP2D63 allele has been assigned as a no function allele by CPIC. Patients carrying the 3 allele in combination with a decreased, normal or no function allele may have decreased metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 3 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of tramadol as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the 3 allele in combination with an increased function allele with an activity value of 3 or greater may have increased metabolism of tramadol 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 tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
110	*2	The CYP2D62 allele is assigned as a normal function allele by CPIC. Patients carrying the 2 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased metabolism of tramadol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the *2 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of tramadol 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 but increased metabolism of tramadol 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. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
109	*1xN	The CYP2D61xN alleles (1x2 and 1x鈮?) are assigned as increased function alleles by CPIC. Patients carrying a 1xN 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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 1xN allele with an activity value of 3 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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 1xN 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 tramadol as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.
108	*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 tramadol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the *1 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased metabolism of tramadol 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 but increased metabolism of tramadol 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. This annotation only covers the pharmacokinetic relationship between CYP2D6 and tramadol and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence tramadol metabolism.

临床证据

id	证据的ID	总结
14698	1451229440	CYP2D6 10/10 is associated with increased exposure to tramadol in healthy individuals as compared to CYP2D6 1 + 2.
14697	1451208380	CYP2D6 3/4 + 4/4 (assigned as poor metabolizer phenotype) are associated with decreased concentrations of o-desmethyltramadol as compared to CYP2D6 1/1 + 1/4 + 1/6 + 1/10 + 4/10 + 10/10.
14696	1451207940	CYP2D6 1/1xN (assigned as ultrarapid metabolizer phenotype) is associated with increased clearance of tramadol in healthy individuals as compared to CYP2D6 1/1 + 1/4 + 1/41 (assigned as normal metabolizer phenotype) .
14695	1451157920	CYP2D6 4/4 (assigned as poor metabolizer genotype phenotype) is associated with decreased metabolism of tramadol as compared to CYP2D6 1/1 + 1/3 + 1/4 + 1/6 + 1/9 + 4/9 (assigned as normal metabolizer genotype phenotype) .
14694	1451157820	CYP2D6 1/1xN is associated with increased metabolism of tramadol in infants as compared to CYP2D6 1/1.
14579	1183618008	CYP2D6 3 is associated with decreased tramadol metabolism when exposed to tramadol as compared to CYP2D6 1.
14578	1183617999	CYP2D6 4 is associated with decreased tramadol metabolism when exposed to tramadol as compared to CYP2D6 1.
14577	1451230640	CYP2D6 poor metabolizers and intermediate metabolizers are associated with increased concentrations of n-desmethyltramadol in people with Neoplasms and Pain as compared to CYP2D6 normal metabolizers.
14576	1451230620	CYP2D6 poor metabolizers and intermediate metabolizers are associated with decreased concentrations of o-desmethyltramadol in people with Neoplasms and Pain as compared to CYP2D6 normal metabolizers.
14575	1451207900	CYP2D6 poor metabolizer is associated with increased exposure to tramadol as compared to CYP2D6 intermediate metabolizer and normal metabolizer.
14574	1451155820	CYP2D6 poor metabolizer phenotype is associated with decreased metabolism of tramadol in healthy individuals as compared to CYP2D6 normal metabolizer phenotype.
14573	1451155560	CYP2D6 poor metabolizer is associated with decreased metabolism of tramadol in healthy individuals as compared to CYP2D6 normal metabolizer.
14572	1451153020	CYP2D6 poor metabolizer phenotype is associated with decreased metabolism of tramadol in healthy individuals as compared to CYP2D6 normal metabolizer phenotype.
14571	1451134168	CYP2D6 poor metabolizers and intermediate metabolizers are associated with decreased concentrations of o-desmethyltramadol in healthy individuals as compared to CYP2D6 normal metabolizers.
14570	1451134163	CYP2D6 poor metabolizers and intermediate metabolizers are associated with increased concentrations of tramadol in healthy individuals as compared to CYP2D6 normal metabolizers.
14569	1449752878	CYP2D6 poor metabolizer is associated with increased concentrations of o-desmethyl-tramadol in people with Low Back Pain and Osteoarthritis as compared to CYP2D6 normal metabolizer.
14568	1449752869	CYP2D6 ultrarapid metabolizer is associated with increased concentrations of o-desmethyl-tramadol in people with Low Back Pain or Osteoarthritis as compared to CYP2D6 normal metabolizer.
14567	1449162774	CYP2D6 poor metabolizer genotype is not associated with exposure to o-desmethyl-tramadol or tramadol as compared to CYP2D6 normal metabolizer genotype.
14566	1449154915	CYP2D6 deficiency is associated with decreased exposure to o-desmethyl-tramadol in infants with Pain.
14565	1446896368	CYP2D6 ultrarapid metabolizer genotype is associated with increased metabolism of tramadol.
14564	1183684661	CYP2D6 normal metabolizer genotype is associated with increased metabolism of tramadol in healthy individuals as compared to CYP2D6 poor metabolizer genotype.
14563	1183684657	CYP2D6 ultra-metabolizer genotype is associated with increased metabolism of tramadol in healthy individuals as compared to CYP2D6 poor metabolizer genotype.
14562	1183684653	CYP2D6 ultra-metabolizer genotype is associated with increased likelihood of nausea when treated with tramadol in healthy individuals as compared to CYP2D6 normal metabolizer genotype.
14561	1183684640	CYP2D6 ultra-metabolizer genotype is associated with increased metabolism of tramadol in healthy individuals as compared to CYP2D6 normal metabolizer genotype.
14560	1183617989	CYP2D6 poor metabolizer is associated with decreased metabolism of tramadol and decreased response to tramadol when treated with tramadol as compared to CYP2D6 normal metabolizer.
14559	PA166104959	Annotation of DPWG Guideline for tramadol and CYP2D6
14558	PA166228101	Annotation of CPIC Guideline for tramadol and CYP2D6
14502	1451565700	CYP2D6 1/5 + 1/10 + 2/5 + 2/10 + 5/10 + 10/10 are associated with increased concentrations of n-desmethyltramadol in people with Head and Neck Neoplasms as compared to CYP2D6 1/1 + 1/2.
14501	1451552540	CYP2D6 1/4 + 1/9 (assigned as intermediate metabolizer genotype phenotype) are associated with increased exposure to tramadol in healthy individuals as compared to CYP2D6 1/1 (assigned as normal metabolizer genotype phenotype) .
14500	1451229680	CYP2D6 4/4 + 4/5 (assigned as poor metabolizer phenotype) are associated with decreased exposure to n,o-didesmethyltramadol or o-desmethyltramadol in healthy individuals as compared to CYP2D6 1/1 + 1/2 + 1/3 + 1/4 + 1/5 + 1/9 + 1/35 + 1/41 + 2/5 + 2/35 + 2/41 + 4/35 + 4/41 (assigned as intermediate metabolizer and normal metabolizer phenotype) .
14499	1451229484	CYP2D6 5/5 + 10/10 are associated with decreased concentrations of n,o-didesmethyltramadol or o-desmethyltramadol in healthy individuals as compared to CYP2D6 1 + 2.
14410	1451157780	CYP2D6 1/3 + 1/4 + 1/5 + 1/6 + 3/3 + 4/4 + 4/5 + 4/10 + 4/41 + 5/41 are associated with decreased metabolism of tramadol in infants as compared to CYP2D6 1/1.
14409	1451156620	CYP2D6 1/1xN is associated with decreased concentrations of tramadol in healthy individuals as compared to CYP2D6 1/2 + 2/4.
14408	1451155780	CYP2D6 4/4 + 4/6 are associated with decreased metabolism of tramadol in healthy individuals as compared to CYP2D6 1/1.
14407	1451154280	CYP2D6 1/4 + 1/5 + 1/9 + 1/10 + 4/10 + 5/10 + 10/10 + 10/17 are associated with decreased clearance of tramadol as compared to CYP2D6 1/1.
14406	1183680395	CYP2D6 4/4 is associated with decreased clearance of tramadol in healthy individuals as compared to CYP2D6 1/1.
14405	1183678588	CYP2D6 17 is associated with decreased clearance of tramadol as compared to CYP2D6 1.
14404	1183678578	CYP2D6 10 is associated with decreased clearance of tramadol as compared to CYP2D6 1.
14403	1183618142	CYP2D6 2/2 is not associated with decreased tramadol clearance in chinese volunteers when treated with tramadol in healthy individuals as compared to CYP2D6 1/1.
14402	1183618134	CYP2D6 2/10 is associated with decreased tramadol clearance in chinese volunteers when treated with tramadol in healthy individuals as compared to CYP2D6 1/1.
14401	1183618125	CYP2D6 10/10 is associated with decreased tramadol clearance in chinese volunteers when treated with tramadol in healthy individuals as compared to CYP2D6 1/1.
14400	1183618024	CYP2D6 4/4 is associated with decreased tramadol metabolism and response when treated with tramadol in healthy individuals as compared to CYP2D6 1/1.
14399	1183618016	CYP2D6 6 is associated with decreased tramadol metabolism when exposed to tramadol as compared to CYP2D6 1.

临床病史

id	类型	评论
208	Update	Minor edits to phenotype descriptions
207	Update	Rewrote phenotype descriptions and added CPIC guideline
206	Update	Added PMID 30051214 to evidence
205	Update	Added PMID 29992026 to evidence
204	Update	Added PMID 29524157 to evidence
203	Update	Added PMID 29196917 to evidence
202	Update	Added PMID 26926096 to evidence and updated phenotype descriptions.
201	Update	Added PMID 25560051 to evidence and updated phenotype descriptions
200	Update	Added PMID 24968714 to evidence
199	Update	Added PMID 18520597 to evidence and updated phenotype descriptions.
77	Update	Added PMID 33131142 to evidence
76	Update	Added PMID 32538291 to evidence and updated phenotype description for *9.
75	Update	Added DPWG guideline as evidence
74	Update	CA score added as part of scoring system release. LOE assigned following curator review.
73	Update	Minor edits to phenotype descriptions
39	Update	Added PMID 18317231 to evidence and added phenotype description for the *41 allele
38	Update	Added PMID 17667796 to evidence and updated phenotype descriptions
37	Update	Added PMID 17175164 to evidence
36	Update	Added PMID 16763825 to evidence
35	Update	Added PMID 15906019 to evidence
34	Create	Created

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