A5067612395- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- Colorectal Cancer Treatments and Studies
- Health Systems, Economic Evaluations, Quality of Life
- Pharmacogenetics and Drug Metabolism
- Hair Growth and Disorders
- Statistical Methods in Clinical Trials
- Multiple Myeloma Research and Treatments
- Pharmacological Effects and Toxicity Studies
- Lung Cancer Treatments and Mutations
- Drug Solubulity and Delivery Systems
- Autoimmune Bullous Skin Diseases
- Receptor Mechanisms and Signaling
- Cutaneous lymphoproliferative disorders research
- Cardiac electrophysiology and arrhythmias
- Protein Interaction Studies and Fluorescence Analysis
- Cancer Genomics and Diagnostics
- Facial Rejuvenation and Surgery Techniques
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Circadian rhythm and melatonin
- Biosimilars and Bioanalytical Methods
- Advanced Drug Delivery Systems
- Ubiquitin and proteasome pathways
- Heart Rate Variability and Autonomic Control
- Advanced Causal Inference Techniques
Pfizer (United States)
2019-2025
University of Michigan
2011-2013
Seoul National University
2010
Abstract Ritlecitinib, an orally available Janus kinase 3 and tyrosine inhibitor being developed for the treatment of alopecia areata (AA), is highly soluble across physiological pH range at therapeutic dose. As such, it expected to dissolve rapidly in any vitro dissolution conditions. However, data showed slower 100-mg capsules, used clinical bioequivalence (BE) study, compared with proposed commercial 50-mg capsules. Hence, a biowaiver lower strength using comparable multimedia based on f2...
Human clearance prediction for small- and macro-molecule drugs was evaluated compared using various scaling methods statistical analysis. is generally well predicted single or multiple species simple allometry macro- small-molecule excreted renally. The error higher hepatically eliminated small-molecules scaling, it appears that the mainly associated with low hepatic extraction ratio (Eh). in human reduced a correction of maximum life span (MLP) brain weight (BRW). both monkey liver blood...
Abstract Ritlecitinib is an orally bioavailable, small molecule that has been approved by the U.S. Food and Drug Administration (FDA) as a once‐daily oral treatment option for people 12 years of age older with severe alopecia areata. This article assessed exposure–response (ER) relationship eyebrow eyelash assessment (EBA/ELA) scores on ritlecitinib compared them to Severity Alopecia Tool (SALT) score (primary endpoint) ER ritlecitinib. EBA ELA both are numeric rating scales (NRS) four...
Objectives: In pediatric population PK (PopPK) model development, sparse data and limited covariate information can prevent accurate estimation for parameters their variability. We explored three methods to utilize prior PopPK development. The objectives are summarize the performance from each method highlight key differences advantages associated with these methods. Methods: A was previously established Drug using samples of adults adolescents two Phase 1, one 2b/3, 3 studies. described...
Ritlecitinib is an oral Janus kinase 3/tyrosine expressed in hepatocellular carcinoma family inhibitor undergoing parallel clinical development for alopecia areata, vitiligo, ulcerative colitis, Crohn's disease, and rheumatoid arthritis.
Alopecia areata (AA) is an autoimmune disease characterized by hair loss that can negatively impact quality of life. AA has a significant pediatric prevalence; however, no systemic treatments are approved for in patients aged < 12 years. Ritlecitinib, JAK3/TEC family kinase inhibitor, to treat adults and adolescents with severe ≥ This study evaluated ritlecitinib pharmacokinetic (PK) parameters safety 6 In this single-group, uncontrolled, open-label study, participants received 20 mg once...
Ritlecitinib, an inhibitor of Janus kinase 3 and hepatocellular carcinoma family kinases, is in development as potential treatment for several inflammatory diseases. In vitro studies presented ritlecitinib hepatic organic cation transporter (OCT) 1, renal transporters OCT2 multidrug toxin extrusion (MATE) proteins 1/2K using multiple substrates, ritlecitinib's major inactive metabolite M2, OCT1. A clinical interaction study with OCT1 drug probe (sumatriptan) relevant biomarkers OCT/MATE was...
As drug development scientists strive to accelerate availability of therapies for patients, model-informed (MIDD) plays an important role in contextualizing existing information and facilitating decision making. This paper describes example MIDD, where modeling simulation informed making the circumstance a combined phase 2b single pivotal study ritlecitinib (JAK3/TEC family kinases inhibitor). Longitudinal exposure–response (ER) was conducted describe efficacy alopecia areata patients. The...
Abstract Ritlecitinib is a selective, covalent, irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine expressed in hepatocellular carcinoma (TEC) family kinases. Pharmacokinetics safety ritlecitinib participants with hepatic (Study 1) or renal 2) impairment were to be characterized from two phase I studies. Due study pause caused by COVID-19 pandemic, 2 healthy participant (HP) cohort was not recruited; however, demography severe closely matched 1 HP cohort. We present results...
studies of formulation performance with
In concentration-QTc modeling, oscillatory functions have been used to characterize biological rhythms in QTc profiles. Fitting such is not always feasible because it requires sufficient electrocardiograph sampling. this study, drug concentration and data were simulated using a published model (oscillatory functions). Then, linear mixed-effect models the fitted evaluated terms of biases, precisions, qualities inferences. The simpler with day time as factor variables provided similar accuracy...
Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that abrocitinib a weak time-dependent cytochrome P450 (CYP) 2C19/3A and inducer CYP1A2/2B6/2C19/3A. To assess potential effect on concomitant medications, drug-drug interaction (DDI) were conducted with sensitive probe substrates these CYP enzymes. The impact hormonal contraceptives (ethinyl estradiol levonorgestrel), as CYP3A...
ABSTRACT The purpose of this study was to determine if the disposition cefadroxil, an α-amino-containing β-lactam antibiotic, changes during lipopolysaccharide (LPS)-induced acute inflammation. Six hours after LPS or saline treatment, mice received 1 nmol/g cefadroxil intravenously along with inulin for glomerular filtration rate (GFR) determination. Serial blood samples, tissue and urine were collected at predetermined time points. In order inflammation-induced in GFR, renal tubular...
Ritlecitinib, an inhibitor of Janus kinase 3 and tyrosine expressed in hepatocellular carcinoma family kinases, is development for inflammatory diseases. This study assessed the impact ritlecitinib on drug transporters using a probe endogenous biomarkers.In vitro transporter-mediated substrate uptake inhibition by its major metabolite were evaluated. Subsequently, clinical interaction was conducted 12 healthy adult participants to assess effect pharmacokinetics rosuvastatin, breast cancer...
PF-05251749 is a dual inhibitor of casein kinase 1 δ/ε, key regulators circadian rhythm. As result its mechanism action, may also change the heart rate corrected QT (QTc) rhythm, which confound detection drug-induced QTc prolongation. In this analysis, nonlinear mixed effect model including multioscillator function was developed in addition to fitting prespecified linear concentration-QTc model, identify liability presence potential rhythm change. The modeling results suggested lack...
Since the first approval for transthyretin amyloid polyneuropathy patients, new formulations and different strength of tafamidis have been developed tested in a population (transthyretin cardiomyopathy). The objective this analysis was to develop unified pharmacokinetic (PK) model tafamidis, which can describe PK various healthy subjects as well patients with TTR amyloidosis, understand effects intrinsic extrinsic factors on variability.Pooled data from 23 clinical studies (17 Phase 1 6 2/3...
2553 Background: Ixazomib citrate is an investigational oral proteasome inhibitor in phase 3 (P3) clinical development. It expected to have a favorable cardiac safety profile based on weak vitro inhibition of the hERG channel (IC50 59.6 μM) and vivo nonclinical data. To confirm, serial PK-matched triplicate electrocardiograms (ECGs) were collected 1 (P1) dose-escalation studies characterize effect active moiety ixazomib (Ix; MLN2238) QTc intervals potentially obviate need for dedicated...