Nedosiran population pharmacokinetic and pharmacodynamic modelling and simulation to guide clinical development and dose selection in patients with primary hyperoxaluria type 1.

ABSTRACT:

Aim

To characterize pharmacokinetic and pharmacodynamic profiles of nedosiran in patients with primary hyperoxaluria type 1 (PH1), identify influential covariates and confirm therapeutic doses.

Methods

A population pharmacokinetic (PK)/pharmacodynamic (PD) (POP-PKPD) model was developed to characterize the concentration-time course of nedosiran and the corresponding effect on 24-h urinary oxalate (U_ox)_. Simulations of dosing to achieve clinically meaningful reduction in U_ox in children, adolescents and adults with PH1 were performed.

Results

Analyses included PK data from 143 healthy participants and PH1/PH2 patients, and PD data from 46 PH1 patients. Nedosiran PK was described by a two-compartment model with dual n-transit absorption

SUBMITTER: Zhang S 

PROVIDER: S-EPMC11602945 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature