可待因,临床注释-2,变异和临床注释数据

可待因

临床注释ID

1183616718

药物名称(英)

codeine

变异单倍型

CYP2D6*1, CYP2D6*1xN, CYP2D6*2, CYP2D6*2xN, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*10, CYP2D6*17, CYP2D6*29, CYP2D6*36, 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

216.0625

PMID计数

计数的证据

表现型

表现型(英)

最新日期

2021/11/1 0:00:00

URL

https://www.pharmgkb.org/clinicalAnnotation/1183616718

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
1338	*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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1337	*36	The CYP2D636 allele has been assigned as a no function allele by CPIC. Patients carrying the 36 allele in combination with a decreased, normal or no function allele may have decreased metabolism of codeine as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying the 36 allele in combination with an increased function allele with an activity value of 2 may have similar metabolism of codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1336	*29	The CYP2D629 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 29 allele in combination with another decreased function allele or a no function allele may have decreased metabolism of codeine as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying the *29 allele in combination with an increased function allele may have increased metabolism of codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1335	*17	The CYP2D617 allele has been assigned as a decreased function allele with an activity score of 0.5 by CPIC. Patients carrying the 17 allele in combination with a decreased or no function allele may have decreased metabolism of codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1334	*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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1333	*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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1332	*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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1331	*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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1330	*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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1329	*2xN	The CYP2D62xN alleles (2x2 and 2x鈮?) are assigned as increased function alleles by CPIC. Patients carrying the 2xN 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 2xN 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a 2xN 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1328	*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 codeine 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 codeine 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 codeine 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 codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1327	*1xN	The CYP2D61xN alleles (1x2 and 1x鈮?) are assigned as increased function alleles by CPIC. Patients carrying the 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 codeine 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 codeine 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 codeine as compared to patients with alleles that result in a normal metabolizer phenotype. This annotation only covers the pharmacokinetic relationship between CYP2D6 and codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.
1326	*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 codeine 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 codeine 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 codeine 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 codeine and does not include evidence about clinical outcomes. Other genetic and clinical factors may also influence codeine metabolism.

临床证据

id	证据的ID	总结
1288	1451156680	CYP2D6 2/2xN is associated with increased metabolism of codeine in women.
1287	1447963867	CYP2D6 *17 is associated with decreased metabolism of codeine in people with Anemia, Sickle Cell.
1286	1184756952	CYP2D6 29/29 is associated with decreased metabolism of codeine or debrisoquine in healthy individuals as compared to CYP2D6 1/1 + 1/2.
1285	1184756913	CYP2D6 5/17 is associated with decreased metabolism of codeine, debrisoquine, dextromethorphan or metoprolol in healthy individuals as compared to CYP2D6 17/17 + 1/1.
1284	1183684584	CYP2D6 17 is associated with decreased clearance of codeine with CYP2D6 allelic isoenzyme purified from baculovirus-mediated insect cells as compared to CYP2D6 1.
1283	1183684576	CYP2D6 2 is associated with decreased clearance of codeine with CYP2D6 allelic isoenzyme purified from baculovirus-mediated insect cells as compared to CYP2D6 1.
1282	1183684566	CYP2D6 10 is associated with decreased clearance of codeine with CYP2D6 allelic isoenzyme purified from baculovirus-mediated insect cells as compared to CYP2D6 1.
1281	1183680992	CYP2D6 1/1 + 1/4 is associated with increased plasma level of morphine when treated with codeine in healthy individuals as compared to CYP2D6 3/4 + 4/4 + 5/5.
1280	1183680624	CYP2D6 1/1 + 1xN/1xN is associated with increased metabolism of codeine in healthy individuals.
1279	1183680618	CYP2D6 4/41 is associated with decreased metabolism of codeine in healthy individuals.
1278	1183680612	CYP2D6 4/6 is associated with decreased metabolism of codeine in healthy individuals.
1277	1183680606	CYP2D6 3/4 is associated with decreased metabolism of codeine in healthy individuals.
1276	1183680593	CYP2D6 4/4 is associated with decreased metabolism of codeine in healthy individuals.
1275	1183678609	CYP2D6 17 is associated with decreased clearance of codeine as compared to CYP2D6 1.
1274	1183678599	CYP2D6 10 is associated with decreased clearance of codeine as compared to CYP2D6 1.
1273	1183678427	CYP2D6 17 is associated with decreased activity of CYP2D6 when assayed with bufuralol or codeine as compared to CYP2D6 1.
1272	1183632366	CYP2D6 4/4 is associated with decreased metabolism of codeine in people with Kidney Failure, Chronic as compared to CYP2D6 1/1 + 1/4.
1271	1183632349	CYP2D6 1/10 + 10/10 is associated with decreased plasma levels of morphine, M3G and M6G levels but not those of codeine when treated with codeine in healthy individuals as compared to CYP2D6 1/1.
1270	1183623185	CYP2D6 36 is associated with decreased codeine metabolism and morphine and glucuronides formation when treated with codeine in healthy individuals as compared to CYP2D6 1/*1.
1269	982047744	CYP2D6 *1xN is associated with increased metabolism of codeine.
1268	982047720	CYP2D6 2/2xN is associated with increased metabolism of codeine.
1267	827566514	CYP2D6 1xN/1 (assigned as ultrarapid metabolizer phenotype phenotype) is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer.
1266	827566506	CYP2D6 2xN/41 (assigned as ultrarapid metabolizer phenotype phenotype) is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer.
1265	827566502	CYP2D6 1xN/41 (assigned as ultrarapid metabolizer phenotype phenotype) is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer.
1264	827566496	CYP2D6 1xN/10 (assigned as ultrarapid metabolizer phenotype phenotype) is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer.
1263	827566510	CYP2D6 1/2xN (assigned as ultrarapid metabolizer phenotype phenotype) is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer.
1262	827641940	Genotype TT is associated with decreased metabolism of codeine in people with Kidney Failure, Chronic as compared to genotypes CC + CT.
1261	1451568920	CYP2D6 poor metabolizer phenotype is associated with decreased exposure to morphine in infants as compared to CYP2D6 normal metabolizer and ultrarapid metabolizer.
1260	1451206040	CYP2D6 poor metabolizers are associated with decreased metabolism of codeine.
1259	1451157860	CYP2D6 ultrarapid metabolizer genotype is associated with increased exposure to morphine in healthy individuals as compared to CYP2D6 normal metabolizer genotype.
1258	1451153620	CYP2D6 poor metabolizer phenotype is associated with decreased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer phenotype.
1257	1451152848	CYP2D6 poor metabolizer phenotype is associated with decreased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer phenotype.
1256	1451152807	CYP2D6 ultrarapid metabolizer phenotype is associated with increased metabolism of codeine in healthy individuals as compared to CYP2D6 normal metabolizer phenotype.
1255	PA166104970	Annotation of DPWG Guideline for codeine and CYP2D6
1254	PA166104996	Annotation of CPIC Guideline for codeine and CYP2D6

临床病史

id	类型	评论
1489	Update	Added PMID 33404848 to evidence
1488	Update	Added DPWG guideline as evidence
1487	Update	CA score added as part of scoring system release. LOE assigned following curator review.
1486	Update	Edited phenotype descriptions
1485	Update	Rewrote phenotype descriptions and added CPIC guideline
1484	Update	CA for codeine and PK evidence
1483	Update	Added PMID 24747667 to evidence
1482	Update	Added PMID 24122716 to evidence
1481	Update	Added PMID 18334103 to evidence
1480	Update	Added PMID 17872605 to evidence
1479	Update	Added PMID 10850391 to evidence
1478	Update	Added PMID 9357098 to evidence and updated phenotype descriptions
1477	Update	Updated wording: metabolizer status "extensive" has been changed to "normal"; added * alleles to "non-functional" and "reduced function" definitions.

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