Loading and maintenance dose algorithms for phenprocoumon and acenocoumarol using patient characteristics and pharmacogenetic data
| Autor: | Schie, R.M.F. van, Wessels, J.A.M., Cessie, S. le, Boer, A. de, Schalekamp, T., Meer, F.J.M. van der, Verhoef, T.I., Meegen, E. van, Rosendaal, F.R., Maitland-van der Zee, A.H., EU-PACT Study Grp |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male CYP2C9 medicine.medical_specialty Genotype Administration Oral Patient characteristics 030204 cardiovascular system & hematology Mixed Function Oxygenases law.invention Toxicology Phenprocoumon 03 medical and health sciences 0302 clinical medicine law Vitamin K Epoxide Reductases Internal medicine medicine Humans Drug Dosage Calculations International Normalized Ratio Aged Cytochrome P-450 CYP2C9 Acenocoumarol Polymorphism Genetic Clinical pharmacology Maintenance dose business.industry Body Weight Anticoagulants Middle Aged Body Height 3. Good health VKORC1 Pharmacogenetics 030220 oncology & carcinogenesis Female Dosing algorithms Aryl Hydrocarbon Hydroxylases Cardiology and Cardiovascular Medicine business Algorithms medicine.drug |
| Zdroj: | European Heart Journal European Heart Journal, 32(15), 1909-1917 European Heart Journal; Vol 32 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Polymorphisms in CYP2C9 and VKORC1 influence patients' phenprocoumon (PHE) and acenocoumarol (ACE) dose requirements. To provide physicians with tools to estimate the patient's individual dose, we aimed to develop algorithms for PHE and ACE.In two Dutch anticoagulation clinics, data on age, sex, height, weight, co-medication, coumarin derivative doses, and international normalized ratio values were obtained from 624 patients taking PHE and 471 taking ACE. Single nucleotide polymorphisms relevant to coumarin derivative dosing on the CYP2C9 and VKORC1 genes were determined. Using multiple linear regression, we developed genotype-guided and non-genotype-guided algorithms to predict the maintenance dose with patient characteristics and genetic information. In addition, loading doses were derived from the calculated maintenance doses. We performed external validation in an independent data set with 229 PHE and 168 ACE users. CYP2C9 and VKORC1 genotype, weight, height, sex, age, and amiodarone use contributed to the maintenance dose of PHE and ACE. The genotype-guided algorithms explained 55.9% (PHE) and 52.6% (ACE) of the variance of the maintenance dose, the non-genetic algorithms 17.3% (PHE) and 23.7% (ACE). Validation in an independent data set resulted in an explained variation of 59.4% (PHE) and 49.0% (ACE) for the genotype-guided algorithms and for 23.5% (PHE) and 17.8% (ACE) for the non-genotype-guided algorithms, without height and weight as parameters.To our knowledge, these are the first genotype-guided loading and maintenance dose algorithms for PHE and ACE using large cohorts. The utility of these algorithms will be tested in randomized controlled trials. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|