The President’s Council of Advisors on Science and Technology (PCAST) recently issued a report to the President of the United States on propelling innovation in drug discovery, development, and evaluation [1]. It is well worth your time to read the entire report. The Council stated that the pace of new therapeutic development has not kept up with the explosion in scientific knowledge of cancer, heart disease, diabetes, and other devastating diseases. Their recommended actions have the audacious goal of doubling, over the next decade, the rate of invention of new medicines for patients, while increasing drug safety.
In Silico Metabolism Webinar
The Metabolism Module in ADMET Predictor™ contains in silico models that classify compounds as substrates and/or inhibitors of the major CYP isoforms, while also predicting likely sites of metabolism and...
Interactions of laulimalide, peloruside, and their derivatives with the isoforms of ß-tubulin
Interactions of laulimalide, peloruside, and their derivatives with the isoforms of β-tubulin.
Predicting Pharmacokinetic Profiles Using In Silico Derived Parameters
Human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential clinical candidates where the accurate estimation of clearance, volume of distribution, bioavailability...
In vitro to in vivo extrapolation and physiologically based modeling of cytochrome P450 mediated metabolism in beagle dog gut wall and liver
The beagle dog is a widely used in vivo model to guide clinical formulation development and to explore the potential for food effects.
Mechanistic Investigation of Negative Food Effect for BCS Class III Compounds in Solid Dosage Forms
Much interest has been expressed in this work on the role of water diffusivity in the release media as a new parameter for predicting drug release.
Things to worry about
Here is computer scientist David Gelernter’s [1] answer to the annual question “2013 : What *Should* We Be Worried About?” at the website Edge [2].
Matched Molecular Pairs Webinar
This webinar describes algorithms for the rapid and automatic extraction of Matched Molecular Pairs (MMPs) from large chemical data sets and for converting these pairs into structural transformation rules that...
Pharmacokinetic Profile of an Ascending-Dose, Estrogen/Progestin Combination Oral Contraceptive
The estrogen component of oral contraceptives provides stability to the endometrium so that irregular shedding and unwanted breakthrough bleeding are minimized. An ascending-dose, extended-regimen…
The PK/PD Relationship of Ethinyl Estradiol and Unscheduled Bleeding or Spotting for an Ascending-dose, Estrogen/Progestin Combination Oral Contraceptive (OC)
The estrogen component of OCs provides stability to the endometrium so that irregular shedding and unwanted breakthrough bleeding are minimized. An ascending-dose, extended-regimen ethinyl estradiol…
Mechanistic Modeling Reveals the Most Important Unknowns in Bile Acid-Mediated DILI
BSEP inhibition and consequent bile acid (BA) buildup has been proposed to be an important mechanism in druginduced liver injury (DILI). There are many gaps in the knowledge of BA homeostasis and its…
Simulations Plus Reports Preliminary Revenues for Second Fiscal Quarter FY2013
Revenues Increase 11.7% for New Record Quarter
DILIsym™, a Mechanistic Model of Drug-Induced Liver Injury, Supports the Interpretation of Elevated Liver Transaminase Levels in a Healthy Volunteer Pooled Safety Population for an Orphan Drug Designed for a Life-Threatening Situation
Compound A is in development for a life-threatening situation. The “Animal Rule” applies to efficacy, but not to safety assessment, which must be determined in humans. In a pooled safety population…
Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug using Lipophilic Fragments Disturbing the Crystal Lattice
Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility.
Predicting Pharmacokinetic Profiles Using in Silico Derived Parameters
Human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential clinical candidates where the accurate estimation of clearance, volume of distribution, bioavailability, and the plasma-concentration- time profiles are the desired end points.
The Drama in Drug Development
In 2005, playwright David Mamet* wrote a memo to the writers of the TV show The Unit that went viral on the internet. I have taken some liberties to adapt the memo to pharmacometricians on drug development teams. If you read the online version of the real memo, you will see that I did not have to do much editing, save for redefining the word “drama.”
Interaction of Silymarin Flavonolignans with Organic Anion Transporting Polypeptides (OATPs)
Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption...
Insight…Inspiration…Innovation
Welcome to the beginning of 2013. Most of us, I bet, had a challenging 2012, certainly it was stressful, but there is so much to be grateful for and, if one is optimistic, there are many opportunities that are full of promise for the New Year.
Three-Dimensional Quantitative Structure–Activity Relationship Analysis of Inhibitors of Human and Rat Cytochrome P4503A Enzymes
Cytochrome P450 3A4 (CYP3A4) is a member of the CYP family and is an important enzyme in drug metabolism.