Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious dose.

ABSTRACT:

Background

Apramycin is under development for human use as EBL-1003, a crystalline free base of apramycin, in face of increasing incidence of multidrug-resistant bacteria. Both toxicity and cross-resistance, commonly seen for other aminoglycosides, appear relatively low owing to its distinct chemical structure.

Objectives

To perform a population pharmacokinetic (PPK) analysis and predict an efficacious dose based on data from a first-in-human Phase I trial.

Methods

The drug was administered intravenously over 30 min in five ascending-dose groups ranging from 0.3 to 30 mg/kg. Plasma and urine samples were collected from 30 healthy volunteers. PPK model development was performed stepwise and the final model was used for PTA analysis.

Results

A mammillary four-com

SUBMITTER: Zhao C 

PROVIDER: S-EPMC9525081 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature