A5081380130- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Advanced Optimization Algorithms Research
- Spectroscopy and Chemometric Analyses
- Statistical Methods in Clinical Trials
- Pharmacovigilance and Adverse Drug Reactions
- Optimal Experimental Design Methods
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Spacecraft and Cryogenic Technologies
- Advanced Multi-Objective Optimization Algorithms
- Iterative Methods for Nonlinear Equations
- Crystallization and Solubility Studies
- Synthesis of β-Lactam Compounds
- Antiplatelet Therapy and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- Advanced Numerical Methods in Computational Mathematics
- Spectroscopy Techniques in Biomedical and Chemical Research
- Advanced Control Systems Optimization
- Inflammatory mediators and NSAID effects
- Blood Coagulation and Thrombosis Mechanisms
- Pharmaceutical studies and practices
Josai International University
2022-2025
AstraZeneca (Sweden)
2021-2025
Weatherford College
2013-2023
ShanghaiTech University
2023
National Institute of Informatics
2020-2021
Uppsala Monitoring Centre
2020-2021
RIKEN Center for Sustainable Resource Science
2021
Seoul National University
2021
Uppsala University
2013-2020
Adama (Israel)
2019
Uncovering safety signals through the collection and assessment of individual case reports remains a core pharmacovigilance activity. Despite widespread use disproportionality analysis in signal detection, recommendations are lacking on minimum size databases or subsets required to yield robust results. This study aims investigate relationship between database robustness analysis, with regards limiting spurious associations. Three types were created from global VigiBase: random (500...
In the treatment of individual patient, a vision is to achieve best possible balance between benefit and harm. Such tailored therapy relies upon identification characterisation risk factors for adverse drug reactions. Information relevant factor considerations can be captured in event reports could utilised statistical signal detection. The aim this study was explore whether screening broad range within global database uncover signals groups Subgroup disproportionality analysis applied 15.4...
The accurate prediction of OATP1B-mediated drug-drug interactions (DDIs) is challenging for drug development. Here, we report a physiologically-based pharmacokinetic (PBPK) model analysis clinical DDI data generated in heathy subjects who received oral doses cyclosporin A (CysA; 20 and 75 mg) as an OATP1B inhibitor, the probe drugs (pitavastatin, rosuvastatin, valsartan). PBPK models CysA compounds were combined assuming inhibition hepatic uptake endogenous coproporphyrin I (CP-I) by CysA....
Telmisartan, a selective inhibitor of angiotensin II receptor type 1 (AT1), demonstrates nonlinear pharmacokinetics (PK) when orally administered in ascending doses to healthy volunteers, but the underlying mechanisms remain unclear. This study presents physiologically based pharmacokinetic model integrated with target-mediated drug disposition (TMDD-PBPK model) explore mechanism its PK. We employed Cluster-Gauss Newton method for top-down analysis, estimating vivo K
Grazoprevir (GZR), a direct-acting agent for hepatitis C virus, is recognized as substrate organic anion transporting polypeptide 1B (OATP1B), cytochrome P450 3A (CYP3A), and P-glycoprotein (P-gp). The objective of the present study was to elucidate contribution these molecules nonlinear pharmacokinetics GZR using physiologically based pharmacokinetic (PBPK) model. Utilizing plasma concentration-time profiles derived from reported dose-escalation (50-800 mg) clinical studies cumulative...
Population model-based (pharmacometric) approaches are widely used for the analyses of phase IIb clinical trial data to increase accuracy dose selection III trials. On other hand, if analysis is based on one selected model, model bias can potentially spoil process. In this paper, four methods that assume a number pre-defined structure candidates, example set dose–response shape functions, and then combine or select those candidate models introduced. The key hypothesis by combining both...
A new algorithm is proposed for simultaneously finding multiple solutions of an underdetermined inverse problem. The was developed ODE parameter identification problem in pharmacokinetics which are interest. proceeds by computing a cluster simultaneously, and more efficient than algorithms that compute one-by-one because it fits the Jacobian collective way using least squares approach. It demonstrated numerically finds accurate suitably distributed, guided priori information on part solution...
Abstract Coproporphyrin I (CP‐I) is an endogenous biomarker supporting the prediction of drug–drug interactions (DDIs) involving hepatic organic anion transporting polypeptide 1B (OATP1B). We previously constructed a physiologically‐based pharmacokinetic (PBPK) model for CP‐I using clinical DDI data with OATP1B inhibitor, rifampicin (RIF). In this study, PBPK parameters were estimated cluster Gauss–Newton method (CGNM), algorithm used to find multiple approximate solutions nonlinear...
Protein C is the zymogen of an anticoagulant serine protease and converted to its active form (activated protein C: APC) by thrombin in presence thrombomodulin. APC plays important role regulating coagulation fibrinolysis inactivating not only blood factors Va VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim present study was examine effect a human product (designated as CTC-111), compared with that heparin, on disseminated intravascular (DIC) induced lipopolysaccharide...
Abstract Parameter estimation problems of mathematical models can often be formulated as nonlinear least squares problems. Typically these are solved numerically using iterative methods. The local minimiser obtained methods usually depends on the choice initial iterate. Thus, estimated parameter and subsequent analyses it depend One way to reduce analysis bias due iterate is repeat algorithm from multiple iterates (i.e. use a multi-start method). However, procedure computationally intensive...
Bosentan is a high-affinity antagonist of endothelin receptors and one the earliest examples for target-mediated drug disposition [a type nonlinear pharmacokinetics (PKs) caused by saturable target binding]. The previous physiologically based PK (PBPK) modeling indicated that PKs bosentan was explainable considering hepatic uptake. However, it remained unexamined to what extent binding contributes bosentan. Here, we developed PBPK model incorporating uptake analyzed clinical data using...
Small interfering RNAs (siRNAs) with N-acetylgalactosamine (GalNAc) conjugation for improved liver uptake represent an emerging class of drugs to treat diseases. Understanding how pharmacokinetics and pharmacodynamics translate is pivotal in vivo study design human dose prediction. However, the literature sparse on translational data this modality, seldom measured. To overcome these difficulties, we collected time-course biomarker 11 GalNAc-siRNAs various species applied...
Abstract Physiologically‐based pharmacokinetic (PBPK) models can be challenging to work with because they have too many parameters identify from observable data. The profile likelihood method help solve this issue by determining parameter identifiability and confidence intervals, but it involves repetitive optimizations that time‐consuming. Cluster Gauss‐Newton (CGNM) is a estimation efficiently searches through wide range of space. In study, we propose approximates the reusing intermediate...
Introduction: Fusion of the fragment crystallizable (Fc) to protein therapeutics is commonly used extend circulation time by enhancing neonatal Fc-receptor (FcRn)-mediated endosomal recycling and slowing renal clearance. This study applied kinetic modeling gain insights into cellular processing contributing observed pharmacokinetic (PK) differences between novel recombinant ADAMTS13 (MDTCS) its Fc-fusion (MDTCS-Fc). Methods: For MDTCS MDTCS-Fc, their plasma PK profiles were obtained at two...
Abstract In drug discovery and development, estimating therapeutic subtherapeutic doses is crucial for designing early‐phase clinical trials, particularly first‐in‐human (FIH) studies. While increasing the in vitro pharmacological potency (lowering K i ) of a compound to its target expected decrease dose, benefit not necessarily clarified. We analyzed , human vivo pharmacokinetics (PK) parameters, therapeutics 144 oral small‐molecule drugs approved Japan (2010–2021). The data on classic were...
Objective To evaluate if previously found associations between low serum bilirubin concentration and kidney function decline is independent of hemoglobin other key confounders. Research design methods Clinical trial data from the SAVOR-TIMI 53 as well UK primary care electronic healthcare records, Practice Datalink (CPRD), were used to construct three cohorts patients at risk chronic disease (CKD). The randomized clinical (RCT) cohort subset consisted 10,555 type-2 diabetic with increased...
Objective To assess the reproducibility and clinical utility of clustering-based subtyping patients with type 2 diabetes (T2D) established cardiovascular (CV) disease. Methods The outcome trial SAVOR-TIMI 53 (n = 16,492) was used. Analyses focused on T2D CV Unsupervised machine learning technique called “k-means clustering” used to divide into subtypes. K-means clustering including HbA1c, age diagnosis, BMI, HOMA2-IR HOMA2-B assign clusters following subtypes: severe insulin deficient...
An in vivo transcription system was developed by coinfection of cells with replication-deficient viral vectors. Recombinant baculovirus (AcT7HCVLuc) and fowlpox virus (FPVT7HCVLuc) carrying a cDNA the hepatitis C (HCV) minigene encoding HCV 5′ untranslated region (UTR), luciferase gene 3′ UTR, including 98 nt extra sequence, under control T7 promoter were constructed. The synthesized various one these two viruses recombinant (AcCAT7) or adenovirus (AdexCAT7) expressing RNA polymerase...
Parameter estimation of a nonlinear model based on maximizing the likelihood using gradient-based numerical optimization methods can often fail due to premature termination algorithm. One reason for such failure is that these cannot distinguish between minimum, maximum, and saddle point; hence, parameters found by algorithms possibly be in any three stationary points surface. We have maximization mixed effects models used pharmaceutical development, algorithm Broyden–Fletcher–Goldfarb–Shanno...