Introduction. Cangrelor is a direct and reversible P2Y12 receptor antagonist that inhibits platelet activation and aggregation, currently approved in adults undergoing percutaneous coronary intervention.
Aims. To characterise the PKPD relationship of cangrelor and provide a basis for extrapolating efficacy from adults to infants and children, as well as defining the dose rationale in these populations.
Methods. Phase I data in healthy adults in conjunction with allometric principles, were used to extrapolate the PK in children and infants. Emax and indirect response models from in vitro experiment were used to describe the onset, maintenance and offset of the effect on platelet aggregation. The final model has been used to simulate treatment response in children following administration of different dosing regimens (1h IV infusion of 0.1 up to 2.0 µg/kg/min).
Results. A weight-banded regimen is proposed for infants and older children, taking into account platelet counts at baseline.
Discussion. This study represents an initial attempt to extrapolate the efficacy of cangrelor from adults to children by integrating PK and PKPD data from various sources. Our results suggest that a dose rationale can be defined for operative settings in infants and children under the assumption of comparable PKPD relationships across the different age groups. In addition, discrepancies between in vitro and in vivo data are caused by experimental protocol conditions, which can be incorporated as covariates to describe and predict the aggregometry response in children based on in vitro data.