Visual predictive check (VPC) plots and conducted bootstrap analysis validated the model.
Normalized body weight was identified as covariate related to enalapril volume of distribution. Transit compartments added using Erlang distribution method to predicted enalapril absorption and enalaprilat formation phases. First-order conditional estimation with interaction was used for parameter estimation.
#ADDITIVE AND PROPORTIONAL ERROR NONMEM WITH RANDOM EFFECT FULL#
A simultaneous semi-mechanistic population-pharmacokinetic model was developed using NONMEM software, which predicted full profile serum and urine concentrations of enalapril and enalaprilat.
Further, a model informed dosage form population-pharmacokinetic analysis was conducted to evaluate differences in pharmacokinetics of enalapril and its active metabolite enalaprilat when prodrug was administered to 24 healthy adults in a crossover, two periods, two treatments, phase I clinical trial using child-appropriate orodispersible mini-tablets (ODMT) and reference (Renitec ®) dosage formulation. The present analysis was conducted to perform a detailed model informed population pharmacokinetic analysis of prodrug enalapril and its active metabolite enalaprilat in serum and urine. 2Center for Clinical Pharmacology, University Hospitals Leuven/KU Leuven, Leuven, BelgiumĮnalapril is recommended as the first line of therapy and is proven to improve survival rates for treatment of Pediatric Heart Failure however, an approved drug and child appropriate dosage formulation is still absent.1Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.Burckhardt 1, Jan de Hoon 2, Stephanie Laer 1 and LENA Consortium Muhammad Faisal 1 *, Willi Cawello 1, Bjoern B.