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A PK-PD model for p...
A PK-PD model for predicting the impact of age, CYP2C9, and VKORC1 genotype on individualization of warfarin therapy
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- Hamberg, Anna Karin (författare)
- Uppsala universitet,Klinisk farmakologi,Pharmacogenetics
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- Dahl, Marja-Liisa (författare)
- Karolinska Institutet,Uppsala universitet,Klinisk farmakologi,Pharmacogenetics
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Barban, M. (författare)
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- Scordo, Maria Gabriella (författare)
- Uppsala universitet,Klinisk farmakologi,Pharmacogenetics
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakologi
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Pengo, V. (författare)
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Padrini, R. (författare)
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- Jonsson, E. Niklas (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2007-02-14
- 2007
- Engelska.
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 81:4, s. 529-538
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The aim of this study was to characterize the relationship between warfarin concentrations and international normalized ratio (INR) response and to identify predictors important for dose individualization. S- and R-warfarin concentrations, INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/pharmacodynamic model in NONMEM. The anticoagulant response was best described by an inhibitory E(MAX) model, with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. CYP2C9 genotype and age were identified as predictors for S-warfarin clearance, and VKORC1 genotype as a predictor for warfarin sensitivity. Predicted INR curves indicate important steady-state differences between patients with different sets of covariates; differences that cannot be foreseen from early INR assessments alone. It is important to account for CYP2C9 and VKORC1 genotypes and age to improve a priori and a posteriori individualization of warfarin therapy.
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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