Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: a comparative study of platelet aggregation response.
Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5 µM adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16 cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5 µM thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5 µM ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP- and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30-50% IPA (0.20 mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75 mg/day) providing similar inhibition.
Vascular Biology Center of Excellence, University of Tennessee Health Science Center , Memphis, TN 38163, USA. ljennings@uthsc.edu
Lisa K
LK
Jennings
Alan D
AD
Michelson
Mary V
MV
Jacoski
Aditya
A
Tyagi
Svetozar
S
Grgurevich
Jennifer S
JS
Li
Picolo Investigators
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects; D002675:Child, Preschool; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D010446:Peptide Fragments; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; C086309:thrombin receptor peptide SFLLRNP; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine