Personalised Warfarin Dosing in Children Post-cardiac Surgery

Autor: Basma Zuheir Al-Metwali, Linda O’Hare, Sanfui Young, Hussain Mulla, Peter Rivers, Larry Goodyer
Rok vydání: 2019
Předmět:
Heart Defects
Congenital
Male
personalised dosing
medicine.medical_specialty
Adolescent
030204 cardiovascular system & hematology
03 medical and health sciences
0302 clinical medicine
Maintenance therapy
Pharmacokinetics
Vitamin K Epoxide Reductases
Personalised dosing
Internal medicine
pharmacodynamics
medicine
Humans
International Normalized Ratio
Postoperative Period
Prospective Studies
Dosing
Cardiac Surgical Procedures
Child
Blood Coagulation
Cytochrome P-450 CYP2C9
Cross-Over Studies
Dose-Response Relationship
Drug
business.industry
Infant
Newborn
Warfarin
Anticoagulants
Infant
Crossover study
warfarin
Pharmacodynamics
Child
Preschool
030220 oncology & carcinogenesis
Pediatrics
Perinatology and Child Health
Female
Original Article
Observational study
VKORC1
Cardiology and Cardiovascular Medicine
business
pharmacokinetics
medicine.drug
Zdroj: Pediatric Cardiology
ISSN: 1432-1971
0172-0643
Popis: Warfarin 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 two 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 crossover 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). In addition, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% versus 47.4% and 83.4% versus 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.
Databáze: OpenAIRE
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