PB0332 - Pharmacokinetics of protein C in neonates with severe congenital protein C deficiency

Background: Protein C concentrate (human) (PC; Baxalta, Inc., a Takeda company) is indicated for the prevention and treatment of venous thromboembolism and purpura fulminans in neonatal, pediatric and adult patients with severe congenital protein C deficiency (SCPCD).

Aims: To evaluate the pharmacokinetics (PK) of PC in neonates with SCPCD.

Methods: Plasma protein C activity data for neonates (≤27 days old) with SCPCD from one prospective and one retrospective PC clinical studies were analyzed using non-compartmental methods. A population PK (popPK) model, previously developed with data from pediatric and adult patients, was used to perform PK simulations for neonatal patients. Observed and simulated plasma protein C activities were compared. This study was funded by Takeda.

Results: Rich PK data were analyzed from two neonates: one female (aged 15 days) and one male (aged 4 days). The observed half-life of protein C activity was approximately 1.5 hours (versus median of 9.8 hours reported for all patients [product label]). The popPK model included these two neonates along with pediatric and adult patients, and showed that older patients have an increased rate of endogenous protein C production and a reduced volume of distribution than younger patients. Also, patients with higher body weight have higher clearance and volume of distribution than those with lower body weight. For additional neonates with sparse PK data, popPK simulations predicted PK data reasonably well, as compared with the observed data.

Conclusion(s): PC is more rapidly cleared in neonates than in older patients (including adults). Despite limited neonatal PK data, the popPK model described neonatal PK reasonably well. Overall, data indicate that the PK of PC show high inter-patient variability and vary substantially between neonates and older patients, confirming that dosing of PC in neonates should be guided by monitoring of protein C activity.