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dc.contributor.authorGoodyer, Larry
dc.contributor.authorRivers, Peter
dc.contributor.authorO'Hare, Linda
dc.contributor.authorYoung, Sanfui
dc.contributor.authorMulla, Hussain
dc.contributor.authorMetwali, B.
dc.date.accessioned2019-10-16T13:27:30Z
dc.date.available2019-10-16T13:27:30Z
dc.date.issued2019-10-05
dc.identifier.citationAl-Metwali, B., Rivers, P., Goodyer, L., O'Hare, L.,Younf, S., Mulla, H. (2019) Personalised warfarin dosing in children post cardiac surgery. Pediatric Cardiology,en
dc.identifier.issn0172-0643
dc.identifier.urihttps://dora.dmu.ac.uk/handle/2086/18631
dc.descriptionopen access articleen
dc.description.abstractWarfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. The study involved 2 groups of children post cardiac surgery: Group 1 were warfarin naïve, in whom loading and maintenance doses were estimated using the model over a 6-month duration and compared to historical case matched controls. Group 2 were already established on maintenance therapy and randomised into a cross-over study comparing the model with conventional maintenance dosing, over a 12-month period. Five patients enrolled in Group 1. Compared to the control group, the median time to achieve the first therapeutic INR was longer (5 vs 2 days), to stable anticoagulation was shorter (29.0 vs 96.5 days), to over-anticoagulation was longer (15.0 vs 4.0 days). Also, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% vs 47.4% and 83.4% vs 62.3%, respectively. Group 2 included 26 patients. No significant differences in INR control were found between model and conventional dosing phases; mean %ITR was 68.82% versus 67.9% (p=0.84) and mean %TTR was 85.47% versus 80.2% (p=0.09), respectively. The results suggest model-based dosing can improve anticoagulation control, particularly when initiating and stabilising warfarin dosing. Larger studies are needed to confirm these findings.en
dc.language.isoenen
dc.publisherSpringeren
dc.subjectwarfarinen
dc.subjectpersonalised dosingen
dc.subjectpharmacokineticsen
dc.subjectpharmacodynamicsen
dc.titlePersonalised warfarin dosing in children post cardiac surgeryen
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1007/s00246-019-02215-y
dc.peerreviewedYesen
dc.funderNo external funderen
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2019-09-21
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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