1) Early examples and proposed approach 2) Fasted vs. fed state model descriptions – where are we today? 3) Case study: positive food effect predictions – input review 4) Case study: negative food effect…
Leveraging PopPK and PBPK Modeling Approaches to Understand Food/PPI Effects
Applying both top-down (PopPK and PBPK) and bottom-up (PBPK) modeling approaches can leverage existing data sets and help prospectively answer questions. Predictions of absorption-related DDIs…
How to Understand Aqueous Ionization and Its Influence on Key Physical Properties of Drugs
Clearing Up Myths About Aqueous Ionization of Drugs, Understanding the pH Dependence of Aqueous Solubility, & Understanding the pH Dependence of Partitioning
A strategy for early risk predictions of clinical drug-drug interactions involving the GastroPlusTM DDI module for time-dependent CYP inhibitors
A set of reference compounds for time-dependent inhibition (TDI) of cytochrome P450 with available literature data for kinact and KI was used to predict clinical implications using the GastroPlusTM software.
A Survey of the Regulatory Requirements for BCS-Based Biowaivers for Solid Oral Dosage Forms by Participating Regulators and Organisations of the International Generic Drug Regulators Programme
The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions.
Discovery PBPK: How to enhance the expected accuracy of bioavailability predictions for NCEs that are not primarily metabolized
In this webinar, we will review the accuracy of purely in silico estimates of bioavailability and the chemistry classification of new chemical entity (NCE) molecules that are easier or harder to...
Experimental versus theoretical log D7.4, pKa and plasma protein binding values for benzodiazepines appearing as new psychoactive substances
The misuse of benzodiazepines as new psychoactive substances is an increasing problem around the world. Basic physicochemical and pharmacokinetic data is required on these substances to interpret and predict their effects upon humans.
In silico prediction coupled with in vitro experiments and absorption modeling to study the inclusion complex of telmisartan with modified beta-cyclodextrin
Telmisartan (TEL) is a poorly bioavailable antihypertensive drug candidate owing to its low solubility in all the biofluids.
Abatacept Population Pharmacokinetics and Exposure-Response Analyses for Dose Recommendation of SC and IV Abatacept in Patients With Psoriatic Arthritis
Both subcutaneous (SC) and intravenous (IV) abatacept, a selective T-cell co-stimulation modulator, are approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) and...
An Introduction to DILIsym® Software, a Mechanistic Mathematical Representation of Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is one of the primary reasons why a new drug candidate may fail during development.
Case Study in Placebo Modeling and Its Effect on Drug Development
ADHD (attention-deficit/hyperactivity disorder) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity associated with clinically significant impairment in functioning.
High-throughput prediction of fraction absorbed and bioavailability in silico
HTPK simulations run using purely in silico property estimates are in reasonable but imperfect agreement with experimental results in humans and rats.
Walt Woltosz on the passing of world-famous astrophysicist, Professor Sir Stephen Hawking
Walt Woltosz, chairman of Simulations Plus Inc., commented on the passing of world-famous astrophysicist, Professor Sir Stephen Hawking...
"Stephen Hawking was a remarkable man and a global scientific leader. But he was also charming and witty, with a nice sense of humor. He would "dance" in his electric wheelchair at festive events, spinning in circles and dazzling all who watched. He made his place in history, along with Newton, Einstein, Bohr, and so many others. He will be missed."
In Silico-In Vitro Extrapolation for Dermal Exposure
Prediction of in vitro dermal delivery and drug in receptor fluid should be done using Nielsen model for vehicle evaporation...
Cosmetics Europe Evaluation of 6 in silico Skin Penetration Models
The Cosmetics Europe (CosEche) ADME Task Force aims to evaluate and develop in silico skin penetration models using relevant measured values.
Mechanistic Modeling Of Mitochondrial Biogenesis Within Dilisym Could Explain Clinically Observed Adaptation Of Serum Alanine Aminotransferase Elevations
Resolution of serum ALT elevations despite continued drug dosing, termed “adaptation”, is commonly observed in clinical trials, but the underlying mechanisms behind this phenomenon remain unclear.
Prediction of the Liver Toxicity of the Endothelin Receptor Antagonists Sitaxsentan and Ambrisentan for the Treatment of Pulmonary Arterial Hypertension with a Quantitative Systems Toxicology Tool (DILIsym)
Sitaxsentan and ambrisentan are highly selective endothelin-1 type A receptor antagonists which were developed for the treatment of pulmonary arterial hypertension.
Applying in silico-in vitro-in vivo extrapolation (IS-IVIVE) techniques to predict exposure and guide risk assessment
Combining QSAR, PBPK, and QST models is a powerful approach to getting more information out of your data investments early in product development.
In Vitro, in Silico, and in Vivo Assessments of Intestinal Precipitation and Its Impact on Bioavailability of a BCS Class 2 Basic Compound
In this study, a multipronged approach of in vitro experiments, in silico simulations, and in vivostudies was developed to evaluate the dissolution, supersaturation, precipitation, and...
Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth
Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders.