Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms
BackgroundDose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1, but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear.MethodsAim was to scrutinize phenprocoumon dose...
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01620/full |
| _version_ | 1818109551902195712 |
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| author | Katharina Luise Schneider Katharina Luise Schneider Melanie Kunst Ann-Kristin Leuchs Miriam Böhme Klaus Weckbecker Kathrin Kastenmüller Markus Bleckwenn Stefan Holdenrieder Christoph Coch Gunther Hartmann Julia Carolin Stingl Julia Carolin Stingl |
| author_facet | Katharina Luise Schneider Katharina Luise Schneider Melanie Kunst Ann-Kristin Leuchs Miriam Böhme Klaus Weckbecker Kathrin Kastenmüller Markus Bleckwenn Stefan Holdenrieder Christoph Coch Gunther Hartmann Julia Carolin Stingl Julia Carolin Stingl |
| author_sort | Katharina Luise Schneider |
| collection | DOAJ |
| description | BackgroundDose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1, but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear.MethodsAim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to CYP2C9 and VKORC1 in a natural cohort of elderly primary care patients. As a subgroup within the IDrug study, phenprocoumon treated patients with at least two INR values within three months before enrollment (n = 209) were analyzed concerning average weekly dose, standard deviation of weekly dose (intra-subject variability), constant dose (yes/no), average INR and TTR grouped by CYP2C9 and VKORC1 (and combinations).ResultsAverage weekly dose per patient was 14.4 ± 5.3 mg, 11.9 ± 4.0 mg and 11.2 ± 4.3 mg in CYP2C9 wildtypes, *2 and *3 carriers (p < .0001) and 16.0 ± 4.2 mg, 13.3 ± 5.1 mg and 8.0 ± 2.7 mg per week in VKORC1 CC, CT and TT genotypes, respectively (p < .0001). Significant differences concerning intra-subject variability were detected among all groups (p < .0001) with the smallest variability in CYP2C9*3 carriers. TTR medians were 75.4%, 79.4% and 100% in wildtypes, *2 and *3 carriers, respectively (p = 0.0464). The proportion of patients with perfect control was highest among *3 carriers, but this result was not significant (p = 0.0713).DiscussionOur analyses support the results of previous investigations regarding genotype-associated dose requirements and raise the hypothesis that dose stability and anticoagulation quality may be increased in CYP2C9*3 carriers. However, our data should be treated cautiously due to the small sample size.Clinical Trial RegistrationGerman Clinical Trials Register, identifier DRKS00006256. |
| first_indexed | 2024-12-11T02:33:04Z |
| format | Article |
| id | doaj.art-1400a9d673574a2892e651ca43b146d3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T02:33:04Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-1400a9d673574a2892e651ca43b146d32022-12-22T01:23:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-01-011010.3389/fphar.2019.01620498424Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 PolymorphismsKatharina Luise Schneider0Katharina Luise Schneider1Melanie Kunst2Ann-Kristin Leuchs3Miriam Böhme4Klaus Weckbecker5Kathrin Kastenmüller6Markus Bleckwenn7Stefan Holdenrieder8Christoph Coch9Gunther Hartmann10Julia Carolin Stingl11Julia Carolin Stingl12Research Division, Federal Institute for Drugs and Medical Devices, Bonn, GermanyCentre for Translational Medicine, Medical Faculty of the University of Bonn, Bonn, GermanyResearch Division, Federal Institute for Drugs and Medical Devices, Bonn, GermanyResearch Division, Federal Institute for Drugs and Medical Devices, Bonn, GermanyResearch Division, Federal Institute for Drugs and Medical Devices, Bonn, GermanyInstitute of General Practice, Medical Faculty of the University of Düsseldorf, Düsseldorf, GermanyInstitute of General Practice and Family Medicine, Medical Faculty of the University of Bonn, Bonn, GermanyInstitute of General Practice and Family Medicine, Medical Faculty of the University of Bonn, Bonn, GermanyInstitute of Laboratory Medicine, German Heart Centre Munich, Munich, GermanyInstitute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty of the University of Bonn, Bonn, GermanyInstitute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty of the University of Bonn, Bonn, GermanyResearch Division, Federal Institute for Drugs and Medical Devices, Bonn, GermanyCentre for Translational Medicine, Medical Faculty of the University of Bonn, Bonn, GermanyBackgroundDose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1, but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear.MethodsAim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to CYP2C9 and VKORC1 in a natural cohort of elderly primary care patients. As a subgroup within the IDrug study, phenprocoumon treated patients with at least two INR values within three months before enrollment (n = 209) were analyzed concerning average weekly dose, standard deviation of weekly dose (intra-subject variability), constant dose (yes/no), average INR and TTR grouped by CYP2C9 and VKORC1 (and combinations).ResultsAverage weekly dose per patient was 14.4 ± 5.3 mg, 11.9 ± 4.0 mg and 11.2 ± 4.3 mg in CYP2C9 wildtypes, *2 and *3 carriers (p < .0001) and 16.0 ± 4.2 mg, 13.3 ± 5.1 mg and 8.0 ± 2.7 mg per week in VKORC1 CC, CT and TT genotypes, respectively (p < .0001). Significant differences concerning intra-subject variability were detected among all groups (p < .0001) with the smallest variability in CYP2C9*3 carriers. TTR medians were 75.4%, 79.4% and 100% in wildtypes, *2 and *3 carriers, respectively (p = 0.0464). The proportion of patients with perfect control was highest among *3 carriers, but this result was not significant (p = 0.0713).DiscussionOur analyses support the results of previous investigations regarding genotype-associated dose requirements and raise the hypothesis that dose stability and anticoagulation quality may be increased in CYP2C9*3 carriers. However, our data should be treated cautiously due to the small sample size.Clinical Trial RegistrationGerman Clinical Trials Register, identifier DRKS00006256.https://www.frontiersin.org/article/10.3389/fphar.2019.01620/fullCYP2C9doseinternational normalized ratiophenprocoumonVKORC1time in therapeutic range |
| spellingShingle | Katharina Luise Schneider Katharina Luise Schneider Melanie Kunst Ann-Kristin Leuchs Miriam Böhme Klaus Weckbecker Kathrin Kastenmüller Markus Bleckwenn Stefan Holdenrieder Christoph Coch Gunther Hartmann Julia Carolin Stingl Julia Carolin Stingl Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms Frontiers in Pharmacology CYP2C9 dose international normalized ratio phenprocoumon VKORC1 time in therapeutic range |
| title | Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms |
| title_full | Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms |
| title_fullStr | Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms |
| title_full_unstemmed | Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms |
| title_short | Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With CYP2C9 and VKORC1 Polymorphisms |
| title_sort | phenprocoumon dose requirements dose stability and time in therapeutic range in elderly patients with cyp2c9 and vkorc1 polymorphisms |
| topic | CYP2C9 dose international normalized ratio phenprocoumon VKORC1 time in therapeutic range |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01620/full |
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