English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Navtemadlin is a potent, selective, orally available inhibitor of murine double minute 2 that restores p53 activity to induce apoptosis in  TP53  wild-type malignancies. Using richly sampled pharmacokinetic (PK) and pharmacodynamic (PD) data from healthy volunteers, a population PK/PD model was developed. A population PK (PPK) model described the PK characteristics of navtemadlin and its major metabolite acyl glucuronide (M1) and quantified enterohepatic recirculation (EHR).  Post hoc  individual PK parameters from this model were coupled with PD data for serum macrophage inhibitory cytokine-1 (MIC-1, GDF15), a cytokine biomarker of p53 activation, to construct a population PK/PD model that described plasma concentration-driven MIC-1 excursions and enabled simulation of the extent and duration of navtemadlin PD effects. The median apparent clearance (CL/F) and apparent central volume (V2/F) of navtemadlin were 36.4 L/hr and 159 L. The typical maximum stimulatory effect (S max ) was close to the median maximum MIC-1 ratio to baseline of 7.29 in observed data. Simulation revealed a dose-dependent increase of MIC-1 with steady state attained in approximately 7 days, in a 7-day-on/21-day-off dose regimen. Elevated MIC-1 concentrations persist through 17–19 days, leaving about 9-11 PD-free days in a 28-day cycle.

A population pharmacokinetic-pharmacodynamic model of navtemadlin, its glucuronide metabolite (M1) and serum macrophage inhibitory cykokine-1 (MIC-1)