Warfarin dose prediction in children using pharmacometric bridging: comparison with published pharmacogenetic dosing algorithms

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Fältnamn	Indikatorer	Metadata
000		05408naa a2200649 4500
001		oai:DiVA.org:uu-197596
003		SwePub
008		130329s2013 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:lup.lub.lu.se:a06e841b-dab9-43c1-8fc0-5fb06203de72
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1975962 URI
024	7	a https://doi.org/10.1007/s00228-012-1466-42 DOI
024	7	a https://lup.lub.lu.se/record/39325022 URI
040		a (SwePub)uud (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Hamberg, Anna-Karin,d 1964-u Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)anham086
245	1 0	a Warfarin dose prediction in children using pharmacometric bridging :b comparison with published pharmacogenetic dosing algorithms
264		c 2013-01-11
264	1	b Springer Science and Business Media LLC,c 2013
338		a electronic2 rdacarrier
500		a Correction in: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY Volume: 69, Issue: 9, Pages: 1737-1737, DOI: 10.1007/s00228-013-1565-x
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng
653		a PK/PD model
653		a Population analysis
653		a Warfarin
653		a Dosing
653		a Children
653		a Genotype
653		a Clinical Pharmacology
653		a Klinisk farmakologi
653		a PK/PD model
653		a Population analysis
653		a Warfarin
653		a Dosing
653		a Children
700	1	a Friberg, Lena Eu Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)lenasimo
700	1	a Hanséus, Katarinau 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, Lund4 aut0 (Swepub:lu)pedi-kha
700	1	a Ekman-Joelsson, Britt-Marieu Drottnings Silvias Barnsjukhus, Sahlgrenska Universitetssjukhuset, Göteborg4 aut
700	1	a Sunnegårdh, Janu Drottnings Silvias Barnsjukhus, Sahlgrenska Universitetssjukhuset, Göteborg4 aut
700	1	a Jonzon, Andersu Uppsala universitet,Pediatrik4 aut0 (Swepub:uu)andersjz
700	1	a Lundell, Bou Astrid Lindgrens Barnsjukhus, Stockholm4 aut
700	1	a Jonsson, E. Niclasu Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut0 (Swepub:uu)niklasjs
700	1	a Wadelius, Miau Uppsala universitet,Klinisk farmakogenomik och osteoporos4 aut0 (Swepub:uu)miawadel
710	2	a Uppsala universitetb Klinisk farmakogenomik och osteoporos4 org
773	0	t European Journal of Clinical Pharmacologyd : Springer Science and Business Media LLCg 69:6, s. 1275-1283q 69:6<1275-1283x 0031-6970x 1432-1041
856	4	u https://uu.diva-portal.org/smash/get/diva2:613631/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://link.springer.com/content/pdf/10.1007%2Fs00228-012-1466-4.pdf
856	4	u http://dx.doi.org/10.1007/s00228-012-1466-4x freey FULLTEXT
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197596
856	4 8	u https://doi.org/10.1007/s00228-012-1466-4
856	4 8	u https://lup.lub.lu.se/record/3932502

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By the author/editor: Hamberg, Anna-Ka ...; Friberg, Lena E; Hanséus, Katarin ...; Ekman-Joelsson, ...; Sunnegårdh, Jan; Jonzon, Anders; show more...; Lundell, Bo; Jonsson, E. Nicl ...; Wadelius, Mia; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Pediatrics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

Articles in the publication: European Journal ...

By the university: Uppsala University; Lund University

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