A5101529218- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Statistical Methods in Clinical Trials
- Pharmacological Effects and Toxicity Studies
- Cancer therapeutics and mechanisms
- Analytical Chemistry and Chromatography
- Analytical Methods in Pharmaceuticals
- Drug-Induced Hepatotoxicity and Protection
- Tuberculosis Research and Epidemiology
- HIV/AIDS drug development and treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Computational Drug Discovery Methods
- Hormonal Regulation and Hypertension
- Synthesis and biological activity
- Pharmacovigilance and Adverse Drug Reactions
- Cholesterol and Lipid Metabolism
- Urban Green Space and Health
- Innovative Microfluidic and Catalytic Techniques Innovation
- Protein Tyrosine Phosphatases
- Pharmacological Effects of Natural Compounds
- Metabolomics and Mass Spectrometry Studies
- Urban Heat Island Mitigation
- ATP Synthase and ATPases Research
- Ethics in Clinical Research
- Urban Agriculture and Sustainability
Osaka University
2024
Chengdu University of Technology
2024
La Roche College
2018-2021
University of Florida
2020
Columbus Oncology and Hematology Associates
2020
Roche (United States)
2016-2017
Vertex Pharmaceuticals (United States)
2015
AstraZeneca (United States)
2015
Daiichi Sankyo (United States)
2015
Genentech
2014
Tuberculosis (TB) remains as a global pandemic that is aggravated by lack of health care, the spread HIV, and emergence multidrug-resistant TB (MDR-TB) extensively drug-resistant (XDR-TB) strains. New anti-TB drugs are urgently required to shorten long 6−12 month treatment regimen battle Mtb We have identified several potent quinoline-based compounds, bearing an isoxazole containing side-chain. The most 7g 13, exhibited submicromolar activity against replicating bacteria (R-TB), with minimum...
Tuberculosis (TB) is presently regarded as one of the most dangerous infective diseases worldwide and major AIDS-associated infections. To shorten current treatment regimen, there an urgent need to identify new anti-TB agents which are active against both replicating TB (R-TB) nonreplicating (NRP-TB). Mefloquine, a well-known antimalarial drug was found possess reasonable activity NRP-TB, accordingly, 30 analogues were synthesized evaluated for their Mycobacterium tuberculosis H(37)Rv. As...
Background: Divarasib, a covalent inhibitor targeting the Kirsten rat sarcoma virus oncogene homologue glycine-to-cysteine mutation at position 12 (KRAS G12C), is currently in clinical development for Non Small Cell Lung Cancer (NSCLC) treatment, with various combination partners, such as Src homology region 2 domain-containing phosphatase-2 (SHP2) migoprotafib. A quantitative systems pharmacology (QSP) model essential to quantitatively assess single-agent and pharmacodynamic (PD) effects...
Cryopreserved human hepatocytes suspended in plasma (HHSHP) represent an integrated metabolic environment for predicting drug-drug interactions (DDIs). In this study, 13 CYP3A reversible and/or time-dependent inhibitors (TDIs) were incubated with HHSHP 20 min over a range of concentrations after which midazolam 1'-hydroxylation was used to measure activity. This single incubation time method yielded IC(50) values the inhibitors. For each inhibitor-victim drug pair, value combined total...
Evaluation of drug-drug interaction (DDI) involving circulating inhibitory metabolites perpetrator drugs has recently drawn more attention from regulatory agencies and pharmaceutical companies. Here, using amiodarone (AMIO) as an example, we demonstrate the use physiologically based pharmacokinetic (PBPK) modeling to assess how a potential metabolite can contribute clinically significant DDIs. Amiodarone was reported increase exposure simvastatin, dextromethorphan, warfarin by 1.2- 2-fold,...
Recent European Medicines Agency (final) and US Food Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug (DDI) potential if present at ≥ 25% of the parent area under time-concentration curve (AUC) (US Administration) or 10% total drug-related AUC (European Agency). To examine application these regulatory recommendations, a group scientists, representing 18 pharmaceutical companies Metabolism...
The International Consortium for Innovation and Quality (IQ) Physiologically Based Pharmacokinetic (PBPK) Modeling Induction Working Group (IWG) conducted a survey across participating companies around general strategies PBPK modeling of induction, including experience with its utility to address various questions, regulatory interactions, acceptance. results highlight areas where is used high confidence identifies opportunities lower further evaluation needed. To enhance the results,...
Cryopreserved human hepatocytes suspended in plasma (HHSHP) have previously provided accurate CYP3A drug-drug interaction (DDI) predictions from a single IC<sub>50</sub> that captures both reversible and time-dependent inhibition. The goal of this study was to compare the accuracy DDI by protein-free hepatocyte system combined with fraction unbound for inhibitor(s) those obtained protein-containing incubations. Seventeen CYP3A, CYP2C9, or CYP2D6 inhibitors were incubated maintenance medium...
This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major (amiodarone, gemfibrozil, sertraline) were systematically evaluated addition to literature review recent examples. The application PBPK modeling drug by parent–metabolite pairs is described guidance on strategic provided.
Ketoconazole is a potent CYP3A inhibitor used to assess the contribution of drug clearance and quantify increase in exposure due strong inhibitor. Physiologically based pharmacokinetic (PBPK) models have been evaluate treatment regimens resulting maximal inhibition by ketoconazole but reached different conclusions. We compare two PBPK ketoconazole-midazolam interaction, model 1 (Chien et al., 2006) 2 implemented Simcyp (version 11), predict 16 published regimens. With use 2, 41% study point...
1-Aminobenzotriazole (ABT) is a non-isoform specific, time-dependent inhibitor of cytochrome P450 (CYP) enzymes used extensively in preclinical studies to determine the relative contribution oxidative metabolism. Although ABT has been widely used, extent and duration its inhibitory effect not well understood. The purpose this study characterize inhibition CYP rats at both hepatic intestinal levels. In vivo using midazolam (p.o. i.v.), as probe for activity, demonstrated that was complete...
Plateable human hepatocytes with plasma were utilized to generate the uptake transporter kinetic data for pravastatin, an organic anion‐transporting polypeptide (OATP) substrate. The active hepatic of pravastatin was determined a J max value 134.4 pmol/min/million cells and K m 76.77 µM in plateable plasma. physiologically‐based pharmacokinetic (PBPK) model incorporation these vitro successfully simulated i.v. profile without applying scaling factor (the mean predicted area under curve (AUC)...
Generating accurate in vitro data is crucial for to vivo extrapolation and pharmacokinetic predictions. The use of human embryonic kidney (HEK) 293 cells overexpressing organic anion transporting polypeptide (OATP) 1B1 OATP1B3 protein-free buffer 100% plasma incubations was explored the uptake four OATP substrates: pravastatin, rosuvastatin, repaglinide, pitavastatin. Differences were observed each parameter [unbound Michaelis constant (<i>K</i><sub>m,u</sub>), <i>V</i><sub>max</sub>,...
Physiologically based pharmacokinetic (PBPK) modeling was used to predict the human pharmacokinetics and drug-drug interaction (DDI) of GDC-2394. PBPK models were developed using in vitro vivo data reflect oral intravenous PK profiles mouse, rat, dog, monkey. The learnings from preclinical applied a model for prospective predictions. predictions within 3-fold clinical first-in-human study, which optimize validate subsequently DDI prediction. Based on majority scenarios CYP3A induction (mRNA...
Abstract Dementia often leads to polypharmacy and increased ADR risk, making recognition vital since People with (PwD) struggle communicate discomfort. This study used the FDA Adverse Event Reporting System (FAERS) database from 2013 2024 extract dementia-related reports. A total of 23,519 reports were analyzed after data cleansing. Missing was addressed using MissForest algorithm refined KNN imputation. Signal detection calculated PRR (Proportional Ratio) for frequently reported drugs ADRs....
Background This study aims to explore the correlation between urban green space coverage and resident health, analyze its underlying mechanisms. Methods Using panel data from 30 provinces in China 2006 2022, which mainly includes coverage, general health of population, air quality, social connectivity. research constructed a fixed effects model perform baseline regression analysis. A series robustness tests, including variable substitution, controlling for geographical differences, regional...