Advertisement

Topics

Application of Physiologically-Based Pharmacokinetic Modeling to Predict Pharmacokinetics in Healthy Japanese Subjects.

08:00 EDT 25th September 2018 | BioPortfolio

Summary of "Application of Physiologically-Based Pharmacokinetic Modeling to Predict Pharmacokinetics in Healthy Japanese Subjects."

Pharmacokinetics (PK) in Japanese healthy subjects were simulated for nine compounds using physiologically based pharmacokinetic (PBPK) models parameterized with physicochemical properties, preclinical absorption, distribution, metabolism, and excretion (ADME) data, and clinical PK data from non-Japanese subjects. For each dosing regimen, 100 virtual trials were simulated and predicted/observed ratios for C and AUC were calculated. As qualification criteria, it was pre-specified that over 80% of simulated trials should demonstrate ratios to observed data ranging from 0.5 to 2.0. Across all compounds and dose regimens studied 93% of simulated C values in Japanese subjects fulfilled the criteria. Similarly for AUC, 77% of single dosing regimens and 100% of multiple dosing regimens fulfilled the criteria. In summary, mechanistically incorporating the appropriate ADME properties into PBPK models followed by qualification using non-Japanese clinical data can predict PK in Japanese population and lead to efficient trial design and conduct of Japanese Phase I studies. This article is protected by copyright. All rights reserved.

Affiliation

Journal Details

This article was published in the following journal.

Name: Clinical pharmacology and therapeutics
ISSN: 1532-6535
Pages:

Links

DeepDyve research library

PubMed Articles [27697 Associated PubMed Articles listed on BioPortfolio]

Physiologically Based Pharmacokinetic Modeling for Trimethoprim and Sulfamethoxazole in Children.

The aims of this study were to (1) determine whether opportunistically collected data can be used to develop physiologically based pharmacokinetic (PBPK) models in pediatric patients; and (2) characte...

Physiologically-Based Pharmacokinetic Modelling to Predict Exposure Differences in Healthy Volunteers and Subjects with Renal Impairment: Ceftazidime Case Study.

Ceftazidime is a widely used β-lactam antibiotic and almost entirely excreted via glomerular filtration in kidney. The objective of this analysis was to assess the ability of physiologically-based ph...

Whole body Physiologically Based Pharmacokinetic Modeling of Trastuzumab and Prediction of Human Pharmacokinetics.

In the current study, we evaluated the pharmacokinetics (PK) of trastuzumab and sought to predict human PK based on animal studies, through the use of optical imaging and a whole-body physiologically ...

A physiologically-based pharmacokinetic model adequately predicted the human pharmacokinetic profiles of YH4808, a novel K-competitive acid blocker.

A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinic...

Development and evaluation of a physiologically-based pharmacokinetic model for predicting the effects of anti-FcRn therapy on the disposition of endogenous IgG in humans.

This work scaled up a previously developed physiologically-based pharmacokinetic (PBPK) model to predict the effects of anti-FcRn agents on the disposition of endogenous IgG in human subjects. Simulat...

Clinical Trials [17181 Associated Clinical Trials listed on BioPortfolio]

Physiologically-based Pharmacokinetic Modeling of Ivermectin in Healthy Human Volunteers

The present study assesses the pharmacokinetic profile of Ivermectin (IVM) in healthy human volunteers and aims to create a physiologically-based pharmacokinetic model. Planned indication ...

Antithrombotics' Therapeutic Optimization in Hospitalized Patients Using Physiologically- and Population-based Pharmacokinetic Modeling

The main goal of the OptimAT study main goal is to validate a PBPK model for 3 direct oral anticoagulants (rivaroxaban, apixaban, dabigatran) and 3 P2Y12 inhibitors (clopidogrel, ticagrelo...

PK of Clindamycin and Trimethoprim-sulfamethoxazole in Infants and Children

Developmental changes in physiology during childhood influence drug dosing. Failure to account for these changes leads to improper dosing, which is associated with decreased drug efficacy ...

Dose Adaptation to Offset the Interaction Between Ticagrelor and Ritonavir by Population-based PK Modeling

Ticagrelor is a new generation antiplatelet agent with higher efficacy as compared to clopidogrel and prasugrel in treatment of patients with moderate and high ischemic risks. Ticagrelor i...

Population Pharmacokinetic Modeling to Optimize the Dosage of the Piperacillin / Tazobactam Combination in Patients With Sepsis in Intensive Care

Population pharmacokinetic modeling mathematically describes the pharmacokinetics of a drug and the variables likely to influence it in a "typical" patient population. We propose to model ...

Medical and Biotech [MESH] Definitions

The development and application of computational models of human pathophysiology that are individualized to patient-specific data.

The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples.

Computer-based systems that enable management to interrogate the computer on an ad hoc basis for various kinds of information in the organization, which predict the effect of potential decisions.

Laboratory tests demonstrating the presence of physiologically significant substances in the blood, urine, tissue, and body fluids with application to the diagnosis or therapy of disease.

Healthy People Programs are a set of health objectives to be used by governments, communities, professional organizations, and others to help develop programs to improve health. It builds on initiatives pursued over the past two decades beginning with the 1979 Surgeon General's Report, Healthy People, Healthy People 2000: National Health Promotion and Disease Prevention Objectives, and Healthy People 2010. These established national health objectives and served as the basis for the development of state and community plans. These are administered by the Office of Disease Prevention and Health Promotion (ODPHP). Similar programs are conducted by other national governments.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...


Searches Linking to this Article