Here is a number that should stop any oral drug program cold. A compound absorbs at 63% in rats and 3% in humans. Same molecule, same route, a twenty-fold collapse the moment it crossed from the animal to the person. That is pomaglumetad, and species differences in drug absorption turned a preclinical success into a […]
Species Differences in Drug Absorption: The 63% That Became 3% Read More »
Ester prodrug design is an exercise in controlled instability. You start with a molecule that has a real liability: poor solubility, weak permeability, a bitter taste, a short half-life. Then you attach a chemical group that the body will remove at the right time and place. The ester bond is the workhorse of that strategy,
Ester Prodrug Design for the Human Gut, Not the Cancer Line Read More »
The Biopharmaceutics Classification System is one of the most useful shorthand tools in drug development. Two axes, solubility and permeability, sort a compound into one of four classes and shape decisions from formulation to biowaivers. That usefulness is exactly why an error in the inputs is dangerous. When BCS classification permeability comes from a model
How a Bad Esterase Profile Distorts BCS Classification Read More »
Most people treat esterase hydrolysis as a single number. You put an ester-containing compound in front of a model, watch it disappear, and record a rate. That habit hides the fact that carboxylesterase drug metabolism is not one process. It is two enzymes with different jobs and different addresses. Which one your compound meets first
CES1 vs CES2: The Two Enzymes That Decide Carboxylesterase Drug Metabolism Read More »