Mechanistic Model-Based Analysis of Biopharmaceutics Experiments – Application of In Vitro in Vivo Extrapolation (IVIV_E) Techniques Within A PBPK Modelling Framework

In vitro dissolution testing is a critical component of drug product development and is often used as a surrogate for in vivo performance. While the range of (USP) standard methods have been developed and tested for many years, no single dissolution test or apparatus comprehensively maps the in vivo behaviour of the range of compound […]

Read More
Topics:

An Integrated Approach to Mechanistically Model In Vitro Experiments and Incorporate Drug-specific Parameter Estimates within a PBPK Framework to Simulate In-Vivo Drug Dissolution

In vitro dissolution testing is a critical component of drug product development programs and is often used as a surrogate for in vivo performance. Consequently, mechanistic modelling of in vitro dissolution studies and informed data interpretation early in the formulation development process is crucial. The Simcyp In Vitro (Data) Analysis (SIVA) toolkit is a standalone […]

Read More
Topics:

Physiologically-Based Pharmacokinetic (PBPK) Modelling Approach for the Prediction of Small Intestinal Precipitation of Poorly Soluble Drugs – A Simulation Study of Posaconazole Using the Simcyp ADAM Model

Weakly basic poorly soluble drug compounds, such as posaconazole (POSA), may dissolve completely at fasted gastric pH but precipitate upon transit to higher small intestinal pH. A number of in vitro and in vivo methods have been used to study intestinal precipitation of poorly soluble drug compounds with a varying degree of complexity. This research […]

Read More
Topics:

How Does the In Vivo Biliary Elimination of Drugs Change with Age? Evidence from In Vitro and Clinical Data Using a Systems Pharmacology Approach

Information on the developmental changes in biliary excretion (BE) of drugs is sparse. The aims of this study were to collate literature data on the pharmacokinetics of biliary excretion of drugs used in pediatrics and to apply a physiologically-based pharmacokinetic (PBPK) model to predict their systemic clearance (CL) with a view to elucidating age-related changes […]

Read More
Topics:

Prediction of Drug-drug Interactions Arising From CYP3A Induction Using a Physiologically-based Dynamic Model

Using physiologically-based pharmacokinetic modeling, we predicted the magnitude of drug-drug interactions (DDIs) for studies with rifampicin and seven CYP3A4 probe substrates administered i.v. (10 studies) or orally (19 studies). The results showed a tendency to underpredict the DDI magnitude when the victim drug was administered orally. Possible sources of inaccuracy were investigated systematically to determine […]

Read More
Topics:

Metformin and Cimetidine: Physiologically-based Pharmacokinetic Modeling to Investigate Transporter Mediated Drug-drug Interactions

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically–based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney […]

Read More
Topics:

Recent Advances in Development and Application of Physiologically-based Pharmacokinetic (PBPK) Models: A Transition from Academic Curiosity to Regulatory Acceptance

There is a renewed surge of interest in applications of physiologically-based pharmacokinetic (PBPK) models by the pharmaceutical industry and regulatory agencies. Developing PBPK models within a systems pharmacology context allows separation of the parameters pertaining to the animal or human body (the system) from that of the drug and the study design which is essential to develop […]

Read More
Topics:

Development of a Permeability-limited Model of the Human Brain and Cerebrospinal Fluid (CSF) to Integrate Known Physiological and Biological Knowledge: Estimating Time Varying CSF Drug Concentrations and Their Variability Using In Vitro Data

A 4-compartment permeability-limited brain (4Brain) model consisting of brain blood, brain mass, cranial and spinal cerebrospinal fluid (CSF) compartments has been developed and incorporated into a whole body physiologically-based pharmacokinetic (PBPK) model within the Simcyp Simulator. The model assumptions, structure, governing equations and system parameters are described. The model in particular considers the anatomy and […]

Read More
Topics:

Certara’s Best of Blogs 2015

A selection of short essays from our blog, written to empower our customers with biosimulation and regulatory writing solutions in order to help them solve the toughest drug development problems. Certara staff contributions range in topic from pharmacometrics to systems biology to the growing importance of regulatory writing.

Read More
Topics:

Metformin and cimetidine: Physiologically based pharmacokinetic modeling to investigate transporter mediated drug-drug interactions.

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and […]

Read More
Topics:
Learn More
LinkedIn