Pharmacokinetic/pharmacodynamic analysis of apixaban to determine dosing regimens for pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma treated with asparaginase: analysis from the PREVAPIX study

Authors: Jarugula P, Ajavon-Hartmann T, Obianom O, Ludwig EA, Crevar C, Marchisin D, Wang Z, Chen W, He B, Perera V, Murthy B, Merali S
Conference: ASCPT
Keywords: Acute Lymphoblastic Leukemia, ALL, Apixaban, Asparaginase, LL, Lymphoblastic Lymphoma, pharmacokinetic/pharmacodynamic, PK/PD, pkpd, PREVAPIX Study, Venous thromboembolism, VTE, VTE prevention, VTEp
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction
● Apixaban is an orally active, direct selective inhibitor of coagulation factor Xa (FXa),1 and may be a treatment option for prevention of venous thromboembolism (VTE) in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL)
● The pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban have previously been studied in healthy adults and adult patients2,3
– Apixaban has an oral bioavailability of ~50%, which increases proportionally with dose (2.5–10 mg) in adults4
– Apixaban has a total clearance of ~3.3 L/h, and an ~12-hour half-life in adults4
● Apixaban has been studied using age-appropriate oral formulations using a model developed from 2 Phase 1 pediatric studies (NCT01195727, NCT01707394)
● Dose selection for the pediatric population was targeted to achieve similar plasma exposure as seen in adult patients receiving VTE prevention (VTEp) in pediatric patients

By: Jarugula P, Ajavon-Hartmann T, Obianom O, Elizabeth Ludwig, Crevar C, Marchisin D, Wang Z, Chen W, He B, Perera V, Murthy B, AND Merali S.

Poster presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting; March 22-24, 2023; Atlanta, GA.