Apixaban pharmacodynamic activity in umbilical cord, paediatric, and adult plasma

作者：Yetman Robert J; Barrett Yu Chen; Wang Zhaoqing; Adamczyk Robert; Wang Jessie; Ramacciotti Eduardo; Frost Charles^*

来源：Thrombosis and Haemostasis, 2017, 117(8): 1518-1527.

DOI：10.1160/TH16-06-0423

• Apixaban
• paediatric
• pharmacodynamics

The objective was to characterise apixaban pharmacodynamic (PD) activity in umbilical cord (UC), paediatric, and adult plasma. Plasma was obtained from blood samples from six UC donors, 70 paediatric (neonates [birth-<= 1 month], infants (>1-<= 6 months], toddlers [>6 months-<= 2 years], young children [>2-<= 6 years], children [>6-<= 12 years], adolescents [>12-<= 18 years]), and six adult (19-45 years) subjects. Plasma spiked with apixaban 0 (baseline), 30, or 110 ng/ml was analysed for anti-factor Xa activity, factor X levels, prothrombin time (PT), and modified PT (mPT). Apixaban had similar concentration related effects on anti-factor Xa activity across groups (30 ng/ml: 0.223-0.295IU/nnl; 110 ng/ml: 1.212-1.474 IU/ml). Endogenous baseline factor X levels were 43%-68% lower in plasma from UC and subjects <= 6 months versus adults. Factor Xa inhibition (percentage change from baseline in apparent factor X levels) was similar for both apixaban concentrations across groups, except UC, neonate, and infant groups, which showed greater inhibition vs adults for apixaban 110 ng/ml. Baseline PT and mPT were similar across groups. Apixaban had no effect on PT at the concentrations tested. Apixaban 110 ng/ml prolonged mPT similarly across groups (44.4-53.2 s to 64.5-70.0 s); no prolongation was found with apixaban 30 ng/ml. Apixaban demonstrated consistent concentration-related effects on other PD endpoints in plasma samples from all age groups, except factor Xa inhibition.

• 出版日期2017-8