Why the study?
A safe and efficacious clopidogrel dose in infants is unknown despite low doses achieving platelet inhibition comparable to adults, even though infant CYP2C19 levels do not reach adult levels until >6 months of age.
What is the mechanism explaining the difference in clopidogrel potency and in vivo clearance between infants and adults?
What is the mechanism explaining the difference in clopidogrel potency and in vivo clearance between infants and adults?
This study aims to elucidate the pharmacokinetic mechanisms explaining why infants achieve comparable platelet inhibition to adults despite lower clopidogrel doses and immature CYP2C19 levels.
Supports current infant clopidogrel dosing despite low CYP2C19; challenges maturation models and leaves open prospective validation.
Clopidogrel is indicated for the prevention of thrombotic complications in infants (aged 0 to 12 months) undergoing catheterization and device implant procedures due to congenital heart defects. Clopidogrel requires cytochrome P450 (CYP) 2C19 for conversion to the active metabolite. However, CYP2C19 levels in infants do not reach adult levels until >6 months of age. It is therefore surprising that a 0.2 mg/kg/day clopidogrel dose in infants achieves platelet inhibition comparable to that observed in adults on 75 mg/day (~1 mg/kg/day). A safe and efficacious dose of clopidogrel in infants is still unknown. This study aims to compare clopidogrel in vivo clearance between infants and adults, and determine the mechanism that could explain the difference in potency of clopidogrel in these two populations.
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Kelsey Browder (2019) studied this question.
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