Pharmacogenetics of Oral Anticoagulants
Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which i...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Stehle, Simone [verfasserIn] Kirchheiner, Julia [verfasserIn] Lazar, Andreas [verfasserIn] Fuhr, Uwe [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2008 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Clinical pharmacokinetics - Berlin [u.a.] : Springer, 1976, 47(2008), 9 vom: Sept., Seite 565-594 |
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| Übergeordnetes Werk: |
volume:47 ; year:2008 ; number:9 ; month:09 ; pages:565-594 |
| Links: |
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| DOI / URN: |
10.2165/00003088-200847090-00002 |
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SPR033053626 |
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| 520 | |a Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. | ||
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10.2165/00003088-200847090-00002 doi (DE-627)SPR033053626 (SPR)00003088-200847090-00002-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl 44.40 bkl Stehle, Simone verfasserin aut Pharmacogenetics of Oral Anticoagulants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 Kirchheiner, Julia verfasserin aut Lazar, Andreas verfasserin aut Fuhr, Uwe verfasserin aut Enthalten in Clinical pharmacokinetics Berlin [u.a.] : Springer, 1976 47(2008), 9 vom: Sept., Seite 565-594 (DE-627)327644974 (DE-600)2043781-X 1179-1926 nnns volume:47 year:2008 number:9 month:09 pages:565-594 https://dx.doi.org/10.2165/00003088-200847090-00002 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE 44.40 ASE AR 47 2008 9 09 565-594 |
| spelling |
10.2165/00003088-200847090-00002 doi (DE-627)SPR033053626 (SPR)00003088-200847090-00002-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl 44.40 bkl Stehle, Simone verfasserin aut Pharmacogenetics of Oral Anticoagulants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 Kirchheiner, Julia verfasserin aut Lazar, Andreas verfasserin aut Fuhr, Uwe verfasserin aut Enthalten in Clinical pharmacokinetics Berlin [u.a.] : Springer, 1976 47(2008), 9 vom: Sept., Seite 565-594 (DE-627)327644974 (DE-600)2043781-X 1179-1926 nnns volume:47 year:2008 number:9 month:09 pages:565-594 https://dx.doi.org/10.2165/00003088-200847090-00002 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE 44.40 ASE AR 47 2008 9 09 565-594 |
| allfields_unstemmed |
10.2165/00003088-200847090-00002 doi (DE-627)SPR033053626 (SPR)00003088-200847090-00002-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl 44.40 bkl Stehle, Simone verfasserin aut Pharmacogenetics of Oral Anticoagulants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 Kirchheiner, Julia verfasserin aut Lazar, Andreas verfasserin aut Fuhr, Uwe verfasserin aut Enthalten in Clinical pharmacokinetics Berlin [u.a.] : Springer, 1976 47(2008), 9 vom: Sept., Seite 565-594 (DE-627)327644974 (DE-600)2043781-X 1179-1926 nnns volume:47 year:2008 number:9 month:09 pages:565-594 https://dx.doi.org/10.2165/00003088-200847090-00002 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE 44.40 ASE AR 47 2008 9 09 565-594 |
| allfieldsGer |
10.2165/00003088-200847090-00002 doi (DE-627)SPR033053626 (SPR)00003088-200847090-00002-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl 44.40 bkl Stehle, Simone verfasserin aut Pharmacogenetics of Oral Anticoagulants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 Kirchheiner, Julia verfasserin aut Lazar, Andreas verfasserin aut Fuhr, Uwe verfasserin aut Enthalten in Clinical pharmacokinetics Berlin [u.a.] : Springer, 1976 47(2008), 9 vom: Sept., Seite 565-594 (DE-627)327644974 (DE-600)2043781-X 1179-1926 nnns volume:47 year:2008 number:9 month:09 pages:565-594 https://dx.doi.org/10.2165/00003088-200847090-00002 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE 44.40 ASE AR 47 2008 9 09 565-594 |
| allfieldsSound |
10.2165/00003088-200847090-00002 doi (DE-627)SPR033053626 (SPR)00003088-200847090-00002-e DE-627 ger DE-627 rakwb eng 610 ASE 44.00 bkl 44.40 bkl Stehle, Simone verfasserin aut Pharmacogenetics of Oral Anticoagulants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 Kirchheiner, Julia verfasserin aut Lazar, Andreas verfasserin aut Fuhr, Uwe verfasserin aut Enthalten in Clinical pharmacokinetics Berlin [u.a.] : Springer, 1976 47(2008), 9 vom: Sept., Seite 565-594 (DE-627)327644974 (DE-600)2043781-X 1179-1926 nnns volume:47 year:2008 number:9 month:09 pages:565-594 https://dx.doi.org/10.2165/00003088-200847090-00002 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE 44.40 ASE AR 47 2008 9 09 565-594 |
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Enthalten in Clinical pharmacokinetics 47(2008), 9 vom: Sept., Seite 565-594 volume:47 year:2008 number:9 month:09 pages:565-594 |
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Enthalten in Clinical pharmacokinetics 47(2008), 9 vom: Sept., Seite 565-594 volume:47 year:2008 number:9 month:09 pages:565-594 |
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Stehle, Simone @@aut@@ Kirchheiner, Julia @@aut@@ Lazar, Andreas @@aut@@ Fuhr, Uwe @@aut@@ |
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The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. 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Stehle, Simone |
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Stehle, Simone ddc 610 bkl 44.00 bkl 44.40 misc Warfarin misc International Normalize Ratio misc Oral Anticoagulant misc Warfarin Dose misc Phenprocoumon Pharmacogenetics of Oral Anticoagulants |
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610 ASE 44.00 bkl 44.40 bkl Pharmacogenetics of Oral Anticoagulants Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Oral Anticoagulant (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 Phenprocoumon (dpeaa)DE-He213 |
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pharmacogenetics of oral anticoagulants |
| title_auth |
Pharmacogenetics of Oral Anticoagulants |
| abstract |
Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. |
| abstractGer |
Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. |
| abstract_unstemmed |
Abstract Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. The aim of this review is to systematically extract the published data reporting pharmacogenetic influences on oral anticoagulant therapy and to provide empirical doses for individual genotype combinations. To this end, we extracted all data from clinical studies of warfarin, phenprocoumon and acenocoumarol that reported genetic influences on either the dose demand or adverse drug effects, such as bleeding complications. Data were summarized for each substance, and the relative effect of each relevant gene was calculated across studies, assuming a linear gene-dose effect in Caucasians. Cytochrome P450 (CYP) 2C9, which is the main enzyme for rate-limiting metabolism of oral anticoagulants, had the largest impact on the dose demand. Compared with homozygous carriers of CYP2C9*1, patients homozygous for CYP2C9*3 were estimated to need 3.3-fold lower mean doses of warfarin to achieve the same international normalized ratio, with *2 carriers and heterozygous patients in between. Differences for acenocoumarol and phenprocoumon were 2.5-fold and 1.5-fold, respectively. Homozygosity of the vitamin K epoxide reductase complex subunit 1 (VK0RC1) variant C1173T (*2) allele (VKORC1 is the molecular target of anticoagulant action) was related to 2.4-fold, 1.6-fold and 1.9-fold lower dose requirements compared with the wild-type for warfarin, acenocoumarol and phenprocoumon, respectively. Compared with CYP2C9 and VKORC1 homozygous wild-type individuals, patients with polymorphisms in these genes also more often experience severe overanticoagulation. An empirical dose table, which may be useful as a basis for dose individualization, is presented for the combined CYP2C9/VKORC1 genotypes. Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as γ-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies. |
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Pharmacogenetics of Oral Anticoagulants |
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| score |
7.3985195 |