Model-Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin.

ABSTRACT: Apramycin represents a subclass of aminoglycoside antibiotics that has been shown to evade almost all mechanisms of clinically relevant aminoglycoside resistance. Model-informed drug development may facilitate its transition from preclinical to clinical phase. This study explored the potential of pharmacokinetic/pharmacodynamic (PK/PD) modeling to maximize the use of in vitro time-kill and in vivo preclinical data for prediction of a human efficacious dose (HED) for apramycin. PK model parameters of apramycin from four different species (mouse, rat, guinea pig, and dog) were allometrically scaled to humans. A semimechanistic PK/PD model was developed from the rich in vitro data on four Escherichia coli strains and subsequently the sparse in vivo efficacy data on the same strains were integ

SUBMITTER: Sou T 

PROVIDER: S-EPMC8048880 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature