Related Experiment Video
Updated: Apr 19, 2026
Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry
Published on: November 5, 2019
Prasugrel in children with sickle cell disease: pharmacokinetic and pharmacodynamic data from an open-label,
Lori Styles1, Darell Heiselman, Lori E Heath
1*Children's Hospital and Research Center, Oakland, CA †Eli Lilly and Company, Indianapolis, IN ‡Division of Hematology and Oncology, Departments of Pediatrics and Internal Medicine, University of North Carolina, Chapel Hill, NC §Boston Children's Hospital, Boston, MA ∥Cincinnati Children's Hospital Medical Center, Cincinnati, OH ¶Department of Pediatrics and Child Health, Howard University, Washington, DC #Division of Pediatric Hematology-Oncology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
Introduction:
This phase 2 study was designed to characterize the relationship among prasugrel dose, prasugrel's active metabolite (Pras-AM), and platelet inhibition while evaluating safety in children with sickle cell disease. It was open-label, multicenter, adaptive design, dose ranging, and conducted in 2 parts. Part A: Patients received escalating single doses leading to corresponding increases in Pras-AM exposure and VerifyNow®P2Y12 (VN) platelet inhibition and decreases in VNP2Y12 reaction units and vasodilator-stimulated phosphoprotein platelet reactivity index. Part B: Patients were assigned daily doses (0.06, 0.08, and 0.12 mg/kg) based on VN pharmacodynamic measurements at the start of 2 dosing periods, each 14±4 days. Platelet inhibition was significantly higher at 0.12 mg/kg (56.3%±7.4%; least squares mean±SE) compared with 0.06 mg/kg (33.8%±7.4%) or 0.08 mg/kg (37.9%±5.6%). Patients receiving 0.12 mg/kg achieved ≥30% platelet inhibition; only 1 patient receiving 0.06 mg/kg exceeded 60% platelet inhibition. High interpatient variability in response to prasugrel and the small range of exposures precluded rigorous characterization of the relationship among dose, Pras-AM, and platelet inhibition.
Safety:
No hemorrhagic events occurred in Part A; 3 occurred in Part B, all mild and self-limited.
Conclusions:
Most children with sickle cell disease may achieve clinically relevant platelet inhibition with titration of daily-dose prasugrel.
More Related Videos
07:24A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
05:23Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload
Published on: March 14, 2017