hyzetimibe (HS-25) / Zhejiang Hisun - LARVOL DELTA

Physiologically based pharmacokinetic modelling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe. (PubMed, Eur J Pharm Sci) - "The established PBPK model could describe the concentration-time profiles of hyzetimibe and M1 well with good prediction performance. A fully mechanistic model of enterohepatic recirculation warrants further investigation."

Journal • PK/PD data • Dyslipidemia • Metabolic Disorders

The NPC1L1 Gene Exerts a Notable Impact on the Reduction of Low-Density Lipoprotein Cholesterol in Response to Hyzetimibe: A Factorial-Designed Clinical Trial. (PubMed, Front Pharmacol) - "Qualified patients were randomly assigned to one of six treatments: placebo, hyzetimibe (10 or 20 mg), atorvastatin, and atorvastatin plus hyzetimibe (10 or 20 mg). We also highlight the potential necessity for identifying the appropriate subjects to be treated with ezetimibe. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [CTR20150351]."

Clinical • Journal • Dyslipidemia • Metabolic Disorders

On the population pharmacokinetics and the enterohepatic recirculation of hyzetimibe and its main metabolite in Chinese healthy subjects. (PubMed, Br J Clin Pharmacol) - "We present the first PopPK model describing HS-25 and M1 concentrations simultaneously, with the EHC process considered. The modeling and simulation results could provide reference for the clinical use of HS-25."

Clinical • Journal • PK/PD data • Dyslipidemia • Metabolic Disorders

Pharmacokinetic Study of Oral C-Radiolabeled Hyzetimibe, A New Cholesterol Absorption Inhibitor. (PubMed, Front Pharmacol) - "The changed hydroxyl group in the hyzetimibe structure made it easier for that drug, compared with ezetimibe, to combine with glucuronic acid and subsequently increased the urinary excretion of hyzetimibe vs. ezetimibe. These differences highlight the need to investigate in more detail the different pharmacokinetic impacts on the efficacy and safety of hyzetimibe and ezetimibe."

Journal • PK/PD data • Dyslipidemia

HS-25-C-01: Efficacy and Safety of HS-25 or in Combination With Atorvastatin in Chinese Adults With Primary Hypercholesterolemia (clinicaltrials.gov) - P3; N=720; Active, not recruiting; Sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.

New P3 trial • Biosimilar • Dyslipidemia

Recurrent heat shock impairs the proliferation and differentiation of C2C12 myoblasts. (PubMed, Cell Stress Chaperones) - "...Immunoblot analysis and qPCR demonstrated a significant increase in the baseline expression of HSP25, 70, and 90 (among others) in cells after a single HS (43 °C) for 60 min as a typical HS response...Finally, the cell migration (scratch) assay indicated that the wound closure was significantly delayed in HS cells relative to the control cells. Overall, these results suggest that a repeated HS may perturb the active process of proliferation, motility, and differentiation processes in an in vitro murine myoblast-myotube model."

Journal • Biosimilar

Determinants of rodent longevity in the chaperone-protein degradation network. (PubMed) - Cell Stress Chaperones - "All subterranean-dwelling species had higher levels of proteasome activity and autophagy, possibly linked to having to dig in soils rich in heavy metals and where underground atmospheres have reduced oxygen availability. Even after correcting for phylogenetic relatedness, a significant (p < 0.02) positive correlation between MLSP, HSP25, HSF1, proteasome activity, and autophagy-related protein 12 (ATG12) was observed, suggesting that the proteolytic degradation machinery and maintenance of protein quality play a pivotal role in species longevity among rodents."

Journal • Biosimilar