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Warfarin dose predi...
Warfarin dose prediction in children using pharmacometric bridging : comparison with published pharmacogenetic dosing algorithms
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- Hamberg, Anna-Karin, 1964- (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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- Friberg, Lena E (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Hanséus, Katarina (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Barmhjärtcentrum, Skånes Universietessjukhus, Lund
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- Ekman-Joelsson, Britt-Marie (författare)
- Drottnings Silvias Barnsjukhus, Sahlgrenska Universitetssjukhuset, Göteborg
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- Sunnegårdh, Jan (författare)
- Drottnings Silvias Barnsjukhus, Sahlgrenska Universitetssjukhuset, Göteborg
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- Jonzon, Anders (författare)
- Uppsala universitet,Pediatrik
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- Lundell, Bo (författare)
- Astrid Lindgrens Barnsjukhus, Stockholm
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- Jonsson, E. Niclas (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Wadelius, Mia (författare)
- Uppsala universitet,Klinisk farmakogenomik och osteoporos
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(creator_code:org_t)
- 2013-01-11
- 2013
- Engelska.
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 69:6, s. 1275-1283
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Abstract
Ämnesord
Stäng
- PurposeNumerous studies have investigated causes of warfarin dose variability in adults whereas studies in children are limited both in numbers and size. Mechanism-based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children.MethodAn adult population PK/PD-model for warfarin, with CYP2C9 and VKORC1 genotype, age and target INR as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external dataset of children 0-18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children.ResultsOverall, the bridged model predicted INR response well in 64 warfarin treated Swedish children (median age 4.3 years), but with a tendency to over predict INR in children ≤ 2 years old. The bridged model predicted 20 of 49 children (41%) within ± 20% of actual maintenance dose (median age 7.2 years). In comparison the published dosing algorithms predicted 33-41% of the children within ± 20% of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ± 20% of actual dose to 70%.ConclusionA mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- PK/PD model
- Population analysis
- Warfarin
- Dosing
- Children
- Genotype
- Clinical Pharmacology
- Klinisk farmakologi
- PK/PD model
- Population analysis
- Warfarin
- Dosing
- Children
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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