Nilotinib preclinical pharmacokinetics and practical application toward clinical projections of oral absorption and systemic availability

Nilotinib preclinical pharmacokinetics and practical application toward clinical projections of oral absorption and systemic availability

Authors: Xia B, Heimbach T, He H, Lin TH
Publication: Biopharm Drug Dispos
Software: GastroPlus®

Nilotinib is a highly potent and selective bcr-abl tyrosine kinase inhibitor used for the treatment of patients who are in the chronic and accelerated phases of...

Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling

Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling

Publication: Acta Pharmacol Sin
Software: GastroPlus®

To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition...

Design, Synthesis and Testing of Novel Antimalarial Drug Leads Using in silico Tools

Design, Synthesis and Testing of Novel Antimalarial Drug Leads Using in silico Tools

Conference: ISSX
Software: ADMET Predictor®
Division: Simulations Plus

The World Health Organization has estimated that over 200 million people suffered from malaria in 2010 and that over 600,000 people died from it that year [1]. Growing problems with resistance to existing anti­…

PBPK Model Simulation of CYP3A4 and Transporter Mediated Drug-drug Interactions Involving Erythromycin

PBPK Model Simulation of CYP3A4 and Transporter Mediated Drug-drug Interactions Involving Erythromycin

Conference: AAPS
Software: GastroPlus®
Division: Simulations Plus

Erythromycin, a macrolide antibiotic, is cleared primarily by cytochrome P450-3A4 metabolism to the N-demethylated metabolite and C-formaldehyde. Its uptake into hepatocytes is mediated by organic…

Novel Antimalarial Drug Candidates Generated in silico by Analysis of Public HTS Data

Novel Antimalarial Drug Candidates Generated in silico by Analysis of Public HTS Data

Conference: AAPS
Division: Simulations Plus

Carry out a prospective experiment to demonstrate the ability of in silico drug design tools to design new lead drug candidates from phenotypic screening data.

Prediction of Amoxicillin Pharmacokinetics in Populations with Altered Renal Function

Prediction of Amoxicillin Pharmacokinetics in Populations with Altered Renal Function

Conference: AAPS
Software: GastroPlus®
Division: Simulations Plus

Purpose of the study was to predict amoxicillin pharmacokinetics in populations with altered renal function to further validate an absorption/PBPK model for amoxicillin.

Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin Absorption and Pharmacokinetics

Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin Absorption and Pharmacokinetics

Conference: AAPS
Software: GastroPlus®
Division: Simulations Plus

Purpose of the study was to develop a PBPK model for amoxicillin incorporating saturable transport processes affecting the drug’s absorption and distribution.

PBPK Modeling of Erythromycin Absorption and Disposition Mediated by Transporters in Humans

PBPK Modeling of Erythromycin Absorption and Disposition Mediated by Transporters in Humans

Conference: AAPS
Division: Simulations Plus

Erythromycin, a macrolide antibiotic, is cleared primarily by cytochrome P450-3A4 metabolism. Its uptake into enterocytes and hepatocytes is mediated by organic anion transporter (OAT) and organic anion…

Excellence Is a Team Sport

Excellence Is a Team Sport

Scientific excellence–asking the right question, then designing and conducting a valid study that answers that question and influences future research–is widely accepted as a benchmark for success in research. However, excellence of a more complicated sort is required in Pharma research. For example, excellence in pharmacometric modeling and simulation has to encompass 3 types of excellence: strategic, operational, and technical.

Inventors and innovation

Inventors and innovation

Elmer Sperry (1860-1930) is remembered as the father of cybernetic (feedback control) engineering. He was the author of more than 350 patents in a wide range of fields, and he developed gyro-controlled steering and fire control systems used on Allied warships during World War I and World War II. He was among the first of the independent inventors of the early 20th century to be elected to the National Academy of Sciences (1).

The problem with gaps.

The problem with gaps.

After writing about gap analysis for the Pharma of the Future? blog, I went in search of an example that would illustrate the problem of defining “gaps” and stumbled on a piece called Reading and Guilty Pleasure in the New York Times. The writer, Gary Gutting, describes 2 assumptions underlying the concept of a guilty pleasure: some books are objectively inferior to others, and “better” books are generally not very enjoyable. So, are “better” books actually better? Gutting says that in discussions of this sort, people will often adopt a relativist position:

Mind the gap

Mind the gap

I was talking with a Program Director the other day about an upcoming regulatory filing. She was rightly proud of the clinical pharmacology work that had been completed, but she was also anxious about possible holes in the package. As we talked, I thought about how gap analyses have changed over the years, particularly since modeling and simulation results have come to play a larger part in the Clinical Pharmacology Summary in NDA submissions.