Simulations Plus

Lixivaptan, a vasopressin-2 receptor antagonist, is being developed for the treatment of autosomal-dominant polycystic kidney disease (ADPKD), an orphan disease that is an unmet medical need.

Bile acid transporter inhibition has been shown to be an important mechanism of drug-induced liver injury (DILI), but the biophase responsible for the transporter inhibition is unclear.

A recent bioavailability study raises questions about the universality of the permeability enhancing effect of chitosan on poorly permeable drugs.

In silico pharmacokinetic (PK) simulations are now routinely incorporated into drug development workflows, especially in the later stages.

Extensive progress has been made in identifying mechanisms for dose-dependent drug-induced liver injury (DILI) and in developing screening assays to reduce its incidence.

To quantitatively and mechanistically compare the liver toxicity potential of oral riluzole versus BHV-0223, combining clinical and mechanistic data, using DILIsym.

Dried blood spot (DBS) pharmacokinetic (PK) sampling was investigated as a potential alternative to plasma sampling for Phase 3 verubecestat (MK-8931) trials due to several potential advantages (ie, reduced cost, reduced clinical site burden, and lower blood volume requirements)

Losartan is a selective, competitive angiotensin 11 receptor type 1 (AT1) antagonist for hypertension treatment.

Resolution of elevations of the liver injury biomarker serum ALT despite continued drug dosing, termed “adaptation”, is commonly observed in clinical trials, but the underlying mechanisms behind this phenomenon remain unclear.

Crizotinib and pazopanib are oral receptor tyrosine kinase inhibitors (TKIs).

FMS-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells, and signaling through FLT3 promotes these cells’ proliferation and differentiation.

Non-alcoholic fatty liver disease (NAFLD) is of growing concern, within developed countries, with recent estimates suggesting up to, 30% of the US population may be affected.

Lack of efficacy continues to be a problem in drug development. Piecemeal rules of thumb such as Lipinski’s Rule of Five [1] help avoid compounds likely to be poorly...

Regulatory agencies have encouraged the use of mechanistic absorption (MAM) and physiologically-based pharmacokinetic (PBPK) modeling to reduce both costs and time to market for new and generic drug products.

The BACE inhibitor verubecestat (MK-8931) demonstrated cognitive and functional decline relative to placebo in a 2-year Phase 3 trial of individuals with prodromal AD (APECS; NCT01953601), along with reductions in brain volume and amyloid plaque. Disease progression modeling has demonstrated a lack of dose or exposure dependency in the clinical cognition and function endpoints (see Poster# P1-044)

Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP).

Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP).

Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP). Previously, fremanezumab was found to be effective and…

Compared with adults, children are more susceptible to infections. In paediatric patients with juvenile idiopathic arthritis (JIA), infections are the most commonly reported AEs linked to biologic (b)DMARDs.

Calcitonin gene-related protein (CGRP) is a well-studied neuropeptide that plays an important role in the pathophysiology of migraines, both centrally and peripherally.1,2 Jugular levels of CGRP are increased...