Population pharmacokinetics of enoxaparin in early stage of pediatric liver transplantation

ABSTRACT

Aim

Preventing post liver transplantation (LT) hepatic artery and portal vein thrombosis includes enoxaparin administration. Enoxaparin pharmacokinetics (PK) has not been investigated in children following LT. We described an enoxaparin PK model in 22 children the first week following the LT.

Methods

Anti-Xa activity time-courses were analyzed using a nonlinear mixed effects approach with Monolix version 2016R.

Results

Anti-Xa activity time-courses were well described by a one-compartment model with first order absorption and elimination. Bodyweight prior the surgery (BW_PREOP) and the related postoperative variation (BW(t)) were the main covariates explaining CL and V between subject variabilities. Parameter estimates were CL_i = CL_TYP*(BW_PREOP/70)^3/4; V_i = V_TYP*(BW(t)/70)¹; where typical clearance (CL_TYP) and typical volume of distribution (V_TYP) were 1.23 L.h^-1 and 14.6 L, respectively. Standard dosing regimens of 50 IU/kg/12 h were insufficient to reach the target range of anti-Xa activity of 0.2 to 0.4 IU/mL. Specifically, seven children (32 %) did never attain the target range during the whole period of treatment and all children were at least once under dosed. According to the final results, we simulated individualized dosing regimens within 4 h following the first administration. More than 100 IU/kg/12 h are suggested to reach the target range of anti-Xa activity of 0.2 to 0.4 IU/mL from the first day.

Conclusion

Thanks to this model, the initial and maintenance doses could be assessed to rapidly achieve the target range. Higher doses per kg, especially in youngest children, are suggested.

http://ift.tt/2smWsPW